Combined Modality Research Articles

Flying‐Saucer‐Shaped Nanoheterojunctions with Enhanced Colorectal Tumor Accumulation for Increased Oxidative Stress and Immunometabolic Regulation

AbstractThe treatment outcomes of nanomedicines against colorectal cancer are severely restricted by their insufficient accumulation in the tumor tissues, unsatisfactory antitumor effect, and weak immunometabolic modulation. To address these issues, flying‐saucer‐shaped nanoheterojunctions by coating copper oxide (CuxO) onto the surface of PEGylated zinc oxide (ZnO) nanoparticles are constructed. When exposed to ultrasound, the resultant CuxO@ZnO nanoheterojunctions exhibit increased locomotor activities, facilitating colorectal mucus infiltration, deep tumor penetration, and tumor cell internalization. The decoration of CuxO suppresses the rapid recombination of electrons and holes in CuxO@ZnO exposed to ultrasound, promoting the production of singlet oxygen and hydroxyl radical, which are generated by CuxO through a Fenton‐like chemodynamic reaction and CuxO@ZnO through sonodynamic reaction. After rectal administration, the sono‐chemodynamic CuxO@ZnO plus PD‐L1 antibodies effectively inhibit the growth of orthotopic and distant tumors. It elicits immunometabolic responses by inducing immunogenic cell death, activating the interferon genes signaling pathway stimulator, and inhibiting glucose transport and the glycolytic signaling pathways. This combined modality also increases the proportion of beneficial microbes (e.g., Bifidobacterium) and decreases the abundance of harmful microorganisms (e.g., Romboutsia) in the intestine. This treatment modality (CuxO@ZnO plus ultrasound and PD‐L1 antibodies) is a promising strategy for the synergistic treatment of colorectal cancer.

A Multi-Classification Accessment Framework for Reproducible Evaluation of Multimodal Learning in Alzheimer's Disease.

Multimodal learning is widely used in automated early diagnosis of Alzheimer's disease. However, the current studies are based on an assumption that different modalities can provide more complementary information to help classify the samples from the public dataset Alzheimer's Disease Neuroimaging Initiative (ADNI). In addition, the combination of modalities and different tasks are external factors that affect the performance of multimodal learning. Above all, we summrise three main problems in the early diagnosis of Alzheimer's disease: (i) unimodal vs multimodal; (ii) different combinations of modalities; (iii) classification of different tasks. In this paper, to experimentally verify these three problems, a novel and reproducible multi-classification framework for Alzheimer's disease early automatic diagnosis is proposed to evaluate and verify the above issues. The multi-classification framework contains four layers, two types of feature representation methods, and two types of models to verify these three issues. At the same time, our framework is extensible, that is, it is compatible with new modalities generated by new technologies. Following that, a series of experiments based on the ADNI-1 dataset are conducted and some possible explanations for the early diagnosis of Alzheimer's disease are obtained through multimodal learning. Experimental results show that SNP has the highest accuracy rate of 57.09% in the early diagnosis of Alzheimer's disease. In the modality combination, the addition of Single Nucleotide Polymorphism modality improves the multi-modal machine learning performance by 3% to 7%. Furthermore, we analyse and discuss the most related Region of Interest and Single Nucleotide Polymorphism features of different modalities.

Role of [18F]FDG-PET/CT in Evaluation of Tumor Response to Chemoradiation Therapy for Advanced Colorectal Cancer

Objectives: The objective is to evaluate the efficacy of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) computed tomography (CT) in the evaluation of tumor response to preoperative/palliative chemoradiotherapy (CRT) for advanced colorectal cancer; including metastatic cancer at primary presentation and recurrent cancers with local and/or distant metastasis. Materials and Methods: Fifty patients with advanced rectal cancer underwent two point imaging with 18 FDG PET-CT before and after 3 weeks of completion of preoperative/palliative CRT in between 2016 and 2022. Patients with locally recurrent cancer also underwent radical surgery. The assessment consisted of the evaluation of the following metabolic PET parameters: Maximum standardized uptake value (SUVmax), SUVratio, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Response was assessed among the followed patients using RECIST 1.1 criteria. Observations and Results: There was a significant decline in the mean post therapy SUVmax and SUVratio as compared to baseline (P = 0.0001). Twenty-six out of 50 (52%) patients were classified as responders. A significant decrease in all parameters (SUVmax, SUVratio, TLG, and MTV) from baseline was observed in responders of the study when comparing with nonresponders (P < 0.05). Besides SUVmax and SUVratio, the mean posttherapy TLG was significantly reduced in responders than nonresponders (P = 0.0065). Conclusion: PET-CT is a useful combined anatomic and functional imaging modality in monitoring tumor response to preoperative/palliative CRT in advanced rectal cancer, whether primary or recurrent, including metastatic cancers at presentation. Posttherapy SUV and TLG in particular are significantly associated with treatment response.

On the Way to Curing Advanced-Stage Mycosis Fungoides/Sézary Syndrome

Advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS) have poor prognosis with median survivals of less than 5 years. Although a variety of treatments are approved for MF/SS patients, durable complete remissions (CR) are rare. Advanced-stage MF or SS patients who achieved CR and maintained in CR or stage IA for more than 10 years were identified by a retrospective search of the principal investigator's database. Of 2266 patients diagnosed with MF or SS, 23 patients with advanced-stage MF/SS (6 IIB, 1 IIIB, 5 IVA1, 3 IVA2, 8 IVB) who achieved CR and maintained in CR or stage IA for ≥ 10 years were identified. As final/curative treatment, 11 patients underwent allogeneic stem cell transplantation (SCT). Most patients presented at young age, underwent SCT with reduced intensity conditioning regimen, had matched related donors, and controllable post-transplant graft versus host disease. Eleven patients were treated with TSEB as part of combined modality protocol in 2 patients and debulking therapy before allogeneic SCT in 9 patients. Five stage IIB patients achieved CR with radiotherapy. Four patients with blood involvement were treated with extracorporeal photopheresis (ECP) in combination with long-term antibiotics and immunomodulatory agents. Long-term antibiotics were given to 14 patients. TSEB followed by allogeneic SCT, radiotherapy, ECP plus long-term antibiotics and immunomodulatory agents were the most common curative/final treatments found in our patients. We are reporting the details of our long-term complete responders' treatment course in the hopes of obtaining more cure responses in the future.

Comparative analysis of two different physiotherapy intervention programs in individuals experiencing chronic lower back pain

Background and objectives. Physiotherapy programs in individuals experiencing chronic lower back pain (CLBP) aim to improve function, disabilities from worsening. As per clinical practice guidelines, many methods are applied, such as the McKenzie method, therapeutic exercises, transcutaneous electrical nerve stimulation (TENS), traction, thermotherapy etc. The effectiveness of these methods is supported by a wide range of evidence and studies, making them some of the most diverse and well-established approaches. These physiotherapeutic treatments are combined every day. Therefore, the aim of this research is to provide a comparative investigation on two different physiotherapy programs containing a combination of these treatment modalities in individuals with CLBP. Materials and methods. This research involved 60 patients who were separated into two groups. Group I received the McKenzie treatment method, passive modalities, lumbar traction, and a walking program. Group II received therapeutic exercises, passive modalities, lumbar traction, and a walking program. Both groups underwent treatment for six weeks. Subjects were tested using research instruments at the beginning, at the end of three weeks, and at the end of six weeks of treatment. The evaluation instruments used were the visual analog scale, Finger-to-Floor test, the Oswestry Low Back Pain Disability Questionnaire, and the Rosenberg self-esteem scale. Results. Pain intensity, functional disability, lumbar flexibility, and self-confidence showed greater improvement after six weeks of treatment in both programs (p <0.0001), without any significant statistical difference among the groups (p >0.05). Conclusions. The data obtained from both groups support the effectiveness of both treatment programs and suggest that they can be considered as options for viable programs treatment for patients with CLBP.

Effects of Stem Cell Therapy on Keloid Treatment: A Literature Review

Fibroblasts that produce excess collagen and growth factors play a role in the pathogenesis of keloid formation. In general, keloids are treated with intralesional corticosteroids alone or with a combination of other modalities, but the recurrence rate is still relatively high, so alternative treatments such as stem cells are being investigated, one of which is Mesenchymal Stem Cells (MSC), which have proven to be useful in healing keloids. Therefore, this literature review aims to discuss the effects of stem cell therapy in the treatment of keloids. In this literature review, 36 journals were used that discussed stem cell therapy in the treatment of keloids taken from various journal sources, namely Google Scholar, Pubmed, Medline, Ebsco, Hindawi, and Cochrane which were published within the last 10 years. According to the source, MSC is divided into 2 types, namely Adipose Mesenchymal Stem Cells (AMSC) and Bone Marrow Mesenchymal Stem Cells (BMMSC). In several studies, AMSC is known to reduce the expression of TGF-β1, COL-1, and COL-2 proteins, and has been shown to inhibit the proliferation of fibroblasts in keloid patients. Whereas in the BMMSC study that was applied with Hydroxybutyl chitosan (HBC) and Arg-Gly-Asp (RGD) hydrogels for 7 days, it was shown to significantly reduce nodular collagen fibers (p<0.05). Keloids occur due to excessive production of collagen and are influenced by various factors such as age, gender, skin color, and genetics. Stem cell therapy, such as MSC, has been proven in various studies to be an alternative treatment for keloids

Global prevalence of advanced fibrosis in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Patients with type 2 diabetes mellitus (T2DM) face a heightened susceptibility to advanced fibrosis, a condition linked to adverse clinical outcomes. However, reported data on liver fibrosis severity among individuals with T2DM vary significantly across studies with diverse characteristics. This meta-analysis aimed to estimate the global prevalence of advanced fibrosis among T2DM patients. A comprehensive systematic search of the EMBASE and MEDLINE databases from inception to November 2022 was conducted to identify studies assessing advanced fibrosis in individuals with T2DM. Random-effects models were utilized to calculate point estimates of prevalence, accompanied by 95% confidence interval (CI). Meta-regression with subgroup analysis was employed to address heterogeneity. We identified 113 eligible studies involving 244,858 individuals from 29 countries. Globally, the prevalence of advanced fibrosis among T2DM patients was 19.5% (95% CI 16.8-22.4%). Regionally, the prevalence rates were as follows: 60.5% in West Asia (95% CI 50.3-70.4%), 24.4% in South Asia (95% CI 16.2-33.7%), 20.1% in East Asia (95% CI 14.7-26.1%), 20.0% in Europe (95% CI 15.8-24.6%), 15.8% in North America (95% CI 11.0-21.3%), and 11.3% in South America (95% CI 6.2-17.5%). The prevalence of advanced fibrosis varied notably based on the study setting and diagnostic methodology employed. Meta-regression models highlighted that 45.13% of the observed heterogeneity could be attributed to combined diagnostic modality and study setting. Globally, approximately one fifth of the T2DM population presents advanced fibrosis, with prevalence differing across geographical regions. Our findings underscore the need for effective strategies to alleviate its global burden.

Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection

This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for treating chronic hepatitis B (CHB), and explore combined RNA interference (RNAi) and immune modulatory modalities for better viral control. Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and evaluated. The lipid nanoparticle (LNP) formulation was optimized by adopting HO-PEG2000-DMG lipid and modifying the molar ratio of traditional polyethylene glycol (PEG) lipid in LNP prescriptions. The efficacy and safety of this formulation in delivering siHBV (tLNP/siHBV) along with the mouse IL-2 (mIL-2) mRNA (tLNP/siHBVIL2) were evaluated in the rAAV-HBV1.3 mouse model. A siRNA combination (terms “siHBV”) with a genotypic coverage of 98.55% was selected, chemically modified, and encapsulated within an optimized LNP (tLNP) of high efficacy and security to fabricate a therapeutic formulation for CHB. The results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA (up to 3log10 reduction; vs PBS) in dose- and time-dependent manners at single-dose or multi-dose frequencies, with satisfactory safety profiles. Further studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus, via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4+ and CD8+ T cell responses by expressed mIL-2 protein. By adopting tLNP as nucleic acid nanocarriers, the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV, thus offering a promising translational therapeutic strategy for treating CHB.

Synergistic Cellular Responses Conferred by Concurrent Optical and Magnetic Stimulation Are Attenuated by Simultaneous Exposure to Streptomycin: An Antibiotic Dilemma.

Concurrent optical and magnetic stimulation (COMS) combines extremely low-frequency electromagnetic and light exposure for enhanced wound healing. We investigated the potential mechanistic synergism between the magnetic and light components of COMS by comparing their individual and combined cellular responses. Lone magnetic field exposure produced greater enhancements in cell proliferation than light alone, yet the combined effects of magnetic fields and light were supra-additive of the individual responses. Reactive oxygen species were incrementally reduced by exposure to light, magnetics fields, and their combination, wherein statistical significance was only achieved by the combined COMS modality. By contrast, ATP production was most greatly enhanced by magnetic exposure in combination with light, indicating that mitochondrial respiratory efficiency was improved by the combination of magnetic fields plus light. Protein expression pertaining to cell proliferation was preferentially enhanced by the COMS modality, as were the protein levels of the TRPC1 cation channel that had been previously implicated as part of a calcium-mitochondrial signaling axis invoked by electromagnetic exposure and necessary for proliferation. These results indicate that light facilitates functional synergism with magnetic fields that ultimately impinge on mitochondria-dependent developmental responses. Aminoglycoside antibiotics (AGAs) have been previously shown to inhibit TRPC1-mediated magnetotransduction, whereas their influence over photomodulation has not been explored. Streptomycin applied during exposure to light, magnetic fields, or COMS reduced their respective proliferation enhancements, whereas streptomycin added after the exposure did not. Magnetic field exposure and the COMS modality were capable of partially overcoming the antagonism of proliferation produced by streptomycin treatment, whereas light alone was not. The antagonism of photon-electromagnetic effects by streptomycin implicates TRPC1-mediated calcium entry in both magnetotransduction and photomodulation. Avoiding the prophylactic use of AGAs during COMS therapy will be crucial for maintaining clinical efficacy and is a common concern in most other electromagnetic regenerative paradigms.

Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience.

The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains debatable, and suitable candidates for de-escalation treatment in these patients have not been fully identified. Therefore, the present study aimed to identify high-risk candidates for human papillomavirus (HPV)-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Patients diagnosed with stage III-IVA OPC and treated with a minimum of two cycles of IC followed by CRT, between 2004 and 2020, were retrospectively reviewed. All the patients were restaged according to the American Joint Committee on Cancer, 8th edition. The overall response rate and survival outcomes associated with clinical factors based on HPV status were analyzed using univariate and multivariate analyses. The present study analyzed 105 patients with a median age of 60 years (range, 40-76 years). Among 105 patients, 40 (38.1%) were HPV-negative and 65 (61.9%) HPV-positive. In all patients, survival outcomes were notably poorer in patients aged ≥60 years (P=0.006) and those who did not achieve complete response post-CRT (P<0.001), irrespective of the HPV status. The median relative dose intensity of IC was ≥80%, indicating adequate treatment, regardless of age. In contrast to patients with HPV-negative OPC, age ≥60 years (P=0.011) and T4 stage (P=0.019) emerged as substantial poor prognostic factors for survival outcomes in patients with HPV-positive OPC. Patients with HPV-positive OPC were categorized into three groups based on the number of clinical factors at diagnosis (such as age and T4 stage). The progression-free and overall survival showed significant stratification across each group as the number of high-risk factors increased despite IC and CRT. The findings indicated that patients with these high-risk factors require a cautious therapeutic strategy even when they are diagnosed with HPV-positive OPC, and the role of combined modality, including IC, will need to be investigated in a randomized trial to be routinely incorporated into clinical practice.

Imaging of oral cavity and oropharyngeal masses: clinico-radiologic correlation

BackgroundClinical diagnosis of the masses of the oropharynx and the oral cavity is usually straightforward; however, deep extension of lesions should be assessed by imaging. Thirty patients with suspected masses in oral cavity and oropharynx were enrolled in the present study. Contrast-enhanced CT and MRI were used for imaging of all patients, and superficial ultrasound was used as screening (whether the mass was accessible to ultrasound or not). The aim of this study was to evaluate clinical impact of combined imaging modalities for assessment of intraoral and oropharyngeal masses.ResultsThere was a statistically significant difference between CT and MRI regarding the detected tumor size, lymph node and adjacent structures. CT had a sensitivity of 77.78% and specificity of 75% in the detection of malignancy. A low apparent diffusion coefficient can detect malignancy with 61.11% sensitivity and 91.67% specificity.ConclusionsThe radiographic diagnosis of the oral cavity presents a complex challenge. According to the unique presentation of each patient, combined CT and MRI imaging will enhance the identification and characterization of lesions in the oral cavity and oropharynx. There is a secondary, limited role for ultrasonography.

Miniaturized electromagnetic tracking enables efficient ultrasound-navigated needle insertions

Ultrasound (US) has gained popularity as a guidance modality for percutaneous needle insertions because it is widely available and non-ionizing. However, coordinating scanning and needle insertion still requires significant experience. Current assistance solutions utilize optical or electromagnetic tracking (EMT) technology directly integrated into the US device or probe. This results in specialized devices or introduces additional hardware, limiting the ergonomics of both the scanning and insertion process. We developed the first ultrasound (US) navigation solution designed to be used as a non-permanent accessory for existing US devices while maintaining the ergonomics during the scanning process. A miniaturized EMT source is reversibly attached to the US probe, temporarily creating a combined modality that provides real-time anatomical imaging and instrument tracking at the same time. Studies performed with 11 clinical operators show that the proposed navigation solution can guide needle insertions with a targeting accuracy of about 5 mm, which is comparable to existing approaches and unaffected by repeated attachment and detachment of the miniaturized tracking solution. The assistance proved particularly helpful for non-expert users and needle insertions performed outside of the US plane. The small size and reversible attachability of the proposed navigation solution promises streamlined integration into the clinical workflow and widespread access to US navigated punctures.

Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.

Medulloblastoma is the most frequently encountered malignant brain tumor in the pediatric population. The standard of care currently consists of surgical resection, craniospinal irradiation, and multi-agent chemotherapy. However, despite this combination of multiple aggressive modalities, recurrence of the disease remains a substantial concern, and treatment resistance is a rising issue. The development of this resistance results from the interplay of a myriad of anatomical properties, cellular processes, molecular pathways, and genetic and epigenetic alterations. In fact, several efforts have been directed towards this domain and characterizing the major contributors to this resistance. Herein, this review highlights the different mechanisms that drive relapse and are implicated in the occurrence of treatment resistance and discusses them in the context of the latest molecular-based classification of medulloblastoma. These mechanisms include the impermeability of the blood-brain barrier to drugs, the overactivation of specific molecular pathways, the resistant and multipotent nature of cancer stem cells, intratumoral and intertumoral heterogeneity, and metabolic plasticity. Subsequently, we build on that to explore potential strategies and targeted agents that can abrogate these mechanisms, undermine the development of treatment resistance, and augment medulloblastoma's response to therapeutic modalities.

ATRT-18. ALISERTIB USED IN PEDIATRIC ATRT

Abstract BACKGROUND Atypical rhabdoid tumor (ATRT) is a rare and aggressive primary CNS tumor caused by variants or deletions in the tumor suppressor gene SMARCB1 (aka INI 1). SMARCB1 targets Aurora A kinase (AURKA), an important oncoprotein of the cell cycle. AURKA dysregulation can lead to genomic instability through its oncogenic effects. Alisertib is a selective AURKA inhibitor that has been explored for treatment in various cancers, including pediatric malignancies. METHODS Retrospective chart review of five patients diagnosed with ATRT, treated with Alisertib, at Nicklaus Children’s Hospital from 2019 - 2024. RESULTS of the 5 patients; three were females and two males, with a median age at diagnosis of 2 years. Only one patient had a germline mutation while the rest had somatic mutations. Prior to starting Alisertib therapy, all five patients received chemotherapy per multiple protocols; four patients underwent focal radiation therapy, three patients underwent resection, and two patients underwent tandem autologous transplants. All five patients were treated solely with Alisertib, median dose of 60 mg/m2 PO daily. Two patients had reduced doses during therapy secondary to cytopenia. One patient completed therapy over 13 months with partial response based on imaging. One patient presented progression of disease while on therapy and for that reason treatment was stopped. Three patients continue treatment: two with only Alisertib, one using Avastin and Sirolimus concurrently. CONCLUSIONS Prognosis in patients with ATRT is usually poor given its aggressive nature and high rate of recurrence despite intervention. It is important to note that treatment of ATRT is highly individualized and typically involves a combination of therapeutic modalities. While Alisertib is one of the newest treatment options, there’s limited literature of clinical improvement in patients with ATRT using this treatment. Therefore, further research on novel treatment options is warranted for the future.

Visual Field Prognosis From Macula and Circumpapillary Spectral Domain Optical Coherence Tomography.

To explore the structural-functional loss relationship from optic-nerve-head- and macula-centred spectral-domain (SD) Optical Coherence Tomography (OCT) images in the full spectrum of glaucoma patients using deep-learning methods. A cohort comprising 5238 unique eyes classified as suspects or diagnosed with glaucoma was considered. All patients underwent ophthalmologic examination consisting of standard automated perimetry (SAP), macular OCT, and peri-papillary OCT on the same day. Deep learning models were trained to estimate G-pattern visual field (VF) mean deviation (MD) and cluster MD using retinal thickness maps from seven layers: retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), inner nuclear layer and outer plexiform layer (INL + OPL), outer nuclear layer (ONL), photoreceptors and retinal pigmented epithelium (PR + RPE), choriocapillaris and choroidal stroma (CC + CS), total retinal thickness (RT). The best performance on MD prediction is achieved by RNFL, GCL + IPL and RT layers, with R2 scores of 0.37, 0.33, and 0.31, respectively. Combining macular and peri-papillary scans outperforms single modality prediction, achieving an R2 value of 0.48. Cluster MD predictions show promising results, notably in central clusters, reaching an R2 of 0.56. The combination of multiple modalities, such as optic-nerve-head circular B-scans and retinal thickness maps from macular SD-OCT images, improves the performance of MD and cluster MD prediction. Our proposed model demonstrates the highest level of accuracy in predicting MD in the early-to-mid stages of glaucoma. Objective measures recorded with SD-OCT can optimize the number of visual field tests and improve individualized glaucoma care by adjusting VF testing frequency based on deep-learning estimates of functional damage.

Effects of CE Ferulic® Combined with Microneedling in the Treatment of Pigmentary Disorders: A Monocentric, Split Face, Comparative Study

Pigmentary disorders of the face present a significant challenge in dermatology, impacting the confidence and well-being of affected individuals. Various approaches have been developed to address these concerns, including microneedling and topical vitamin C products. This study involved 15 participants undergoing three treatment sessions over 12 weeks, assessing the efficacy of a combined microneedling and CE Ferulic® serum approach. Clinical evaluation and statistical analysis were conducted before and after the intervention. Significant improvement of akin hyperpigmentation was observed, particularly on the side treated with microneedling and CE Ferulic® serum compared to microneedling alone. The integrated treatment protocol demonstrated a synergistic effect in improving skin texture and appearance. Integrated treatment protocols, such as combining microneedling with CE Ferulic® serum, show promise in managing facial hyperpigmentation disorders. Further research with larger cohorts is warranted to validate these findings and optimize treatment strategies, highlighting the potential of combined therapeutic modalities for achieving optimal clinical outcomes in pigmentary disorder management.

Predicting conversion from mild cognitive impairment to Alzheimer's disease: a multimodal approach.

Successively predicting whether mild cognitive impairment patients will progress to Alzheimer's disease is of significant clinical relevance. This ability may provide information that can be leveraged by emerging intervention approaches and thus mitigate some of the negative effects of the disease. Neuroimaging biomarkers have gained some attention in recent years and may be useful in predicting the conversion of mild cognitive impairment to Alzheimer's disease. We implemented a novel multi-modal approach that allowed us to evaluate the potential of different imaging modalities, both alone and in different degrees of combinations, in predicting the conversion to Alzheimer's disease of mild cognitive impairment patients. We applied this approach to the imaging data from the Alzheimer's Disease Neuroimaging Initiative that is a multi-modal imaging dataset comprised of MRI, Fluorodeoxyglucose PET, Florbetapir PET and diffusion tensor imaging. We included a total of 480 mild cognitive impairment patients that were split into two groups: converted and stable. Imaging data were segmented into atlas-based regions of interest, from which relevant features were extracted for the different imaging modalities and used to construct machine-learning models to classify mild cognitive impairment patients into converted or stable, using each of the different imaging modalities independently. The models were then combined, using a simple weight fusion ensemble strategy, to evaluate the complementarity of different imaging modalities and their contribution to the prediction accuracy of the models. The single-modality findings revealed that the model, utilizing features extracted from Florbetapir PET, demonstrated the highest performance with a balanced accuracy of 83.51%. Concerning multi-modality models, not all combinations enhanced mild cognitive impairment conversion prediction. Notably, the combination of MRI with Fluorodeoxyglucose PET emerged as the most promising, exhibiting an overall improvement in predictive capabilities, achieving a balanced accuracy of 78.43%. This indicates synergy and complementarity between the two imaging modalities in predicting mild cognitive impairment conversion. These findings suggest that β-amyloid accumulation provides robust predictive capabilities, while the combination of multiple imaging modalities has the potential to surpass certain single-modality approaches. Exploring modality-specific biomarkers, we identified the brainstem as a sensitive biomarker for both MRI and Fluorodeoxyglucose PET modalities, implicating its involvement in early Alzheimer's pathology. Notably, the corpus callosum and adjacent cortical regions emerged as potential biomarkers, warranting further study into their role in the early stages of Alzheimer's disease.

Brain age has limited utility as a biomarker for capturing fluid cognition in older individuals.

One well-known biomarker candidate that supposedly helps capture fluid cognition is Brain Age, or a predicted value based on machine-learning models built to predict chronological age from brain MRI. To formally evaluate the utility of Brain Age for capturing fluid cognition, we built 26 age-prediction models for Brain Age based on different combinations of MRI modalities, using the Human Connectome Project in Aging (n=504, 36-100 years old). First, based on commonality analyses, we found a large overlap between Brain Age and chronological age: Brain Age could uniquely add only around 1.6% in explaining variation in fluid cognition over and above chronological age. Second, the age-prediction models that performed better at predicting chronological age did NOT necessarily create better Brain Age for capturing fluid cognition over and above chronological age. Instead, better-performing age-prediction models created Brain Age that overlapped larger with chronological age, up to around 29% out of 32%, in explaining fluid cognition. Third, Brain Age missed around 11% of the total variation in fluid cognition that could have been explained by the brain variation. That is, directly predicting fluid cognition from brain MRI data (instead of relying on Brain Age and chronological age) could lead to around a 1/3-time improvement of the total variation explained. Accordingly, we demonstrated the limited utility of Brain Age as a biomarker for fluid cognition and made some suggestions to ensure the utility of Brain Age in explaining fluid cognition and other phenotypes of interest.

Ruptured pulmonary Echinococcus granulosus cyst: A rare cause of severe pneumogenic sepsis

Parasitic infections by Echinococcus granulosus are rare in Germany, and predominantly affect individuals with a migration background. Liver and lungs are the most commonly affected organs. Pulmonary cysts often remain asymptomatic until rupture, at which point symptoms may manifest. The diagnostic approach typically involves a combination of imaging modalities and serological tests, occasionally supplemented by molecular genetic methods. Given the global movements of migration, considerations of the epidemiology of common diseases in the country of origin should also be taken into account in the differential diagnosis. We present the unusual case of a pneumogenic sepsis in a young man from Syria, where the combination of medical history alongside radiological, serological, and molecular genetic investigations ultimately led to the diagnosis of a severe pulmonary echinococcosis with rupture.

A global multimodal flood event dataset with heterogeneous text and multi-source remote sensing images

ABSTRACT With the increasing frequency of floods, in-depth flood event analyses are essential for effective disaster relief and prevention. Satellite-based flood event datasets have become the primary data source for flood event analyses instead of limited disaster maps due to their enhanced availability. Nevertheless, despite the vast amount of available remote sensing images, existing flood event datasets continue to pose significant challenges in flood event analyses due to the uneven geographical distribution of data, the scarcity of time series data, and the limited availability of flood-related semantic information. There has been a surge in acceptance of deep learning models for flood event analyses, but some existing flood datasets do not align well with model training, and distinguishing flooded areas has proven difficult with limited data modalities and semantic information. Moreover, efficient retrieval and pre-screening of flood-related imagery from vast satellite data impose notable obstacles, particularly within large-scale analyses. To address these issues, we propose a Multimodal Flood Event Dataset (MFED) for deep-learning-based flood event analyses and data retrieval. It consists of 18 years of multi-source remote sensing imagery and heterogeneous textual information covering flood-prone areas worldwide. Incorporating optical and radar imagery can exploit the correlation and complementarity between distinct image modalities to capture the pixel features in flood imagery. It is worth noting that text modality data, including auxiliary hydrological information extracted from the Global Flood Database and text information refined from online news records, can also offer a semantic supplement to the images for flood event retrieval and analysis. To verify the applicability of the MFED in deep learning models, we carried out experiments with different models using a single modality and different combinations of modalities, which fully verified the effectiveness of the dataset. Furthermore, we also verify the efficiency of the MFED in comparative experiments with existing multimodal datasets and diverse neural network structures.