Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-dimensional template combined with MR-guided iodine-125 brachytherapy for recurrent brain metastases

Purpose Treatment of recurrent brain metastases is extremely challenging. Here, we evaluated the feasibility and efficacy of an individualized three-dimensional template combined with MR-guided iodine-125 (125I) brachytherapy in the treatment of recurrent brain metastases. Material and methods Twenty-eight patients with recurrent 38 brain metastases underwent 125I brachytherapy from December, 2017 to January, 2021. A pre-treatment brachytherapy plan and three-dimensional template were generated according to isovoxel T1-weighted MR images. 125I seeds were implanted under the guidance of three-dimensional template and 1.0-T open MR imaging. Dosimetry verification was performed based on CT/MR fusion images. Pre-operative and post-operative dosimetry parameters of D90, V100, and conformity index (CI) were compared. Overall response rate (ORR), disease control rate (DCR) at 6 months, and 1-year survival rate were calculated. Median overall survival (OS) measured from the date of 125I brachytherapy was estimated using Kaplan-Meier method. Results No significant differences were observed between pre-operative and post-operative D90, V100, and CI values (p > 0.05). The ORR and DCR at 6 months were 91.3% and 95.7%, respectively. The 1-year survival rate was 57.1%. The median OS was 14.1 months. Two cases of minor hemorrhage and 5 cases of symptomatic brain edema were observed during the study. All clinical symptoms were alleviated after corticosteroid treatment applied for 7 to 14 days. Conclusions A three-dimensional template combined with MR-guided 125I brachytherapy in the treatment of recurrent brain metastases is feasible, safe, and effective. This novel 125I brachytherapy strategy is an attractive alternative in the treatment of brain metastases.
Immune Checkpoint Inhibitors as a Treatment Option for Bladder Cancer: Current Evidence

Bladder cancer is a prevalent disease, and treatment options for advanced bladder cancer remain limited. However, immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) have shown promise in treating bladder cancer. These drugs work by blocking receptors and ligands, disrupting signaling, and allowing T cells to recognize and attack cancer cells. ICIs have been found to be effective in treating bladder cancer, especially in cases of metastatic urothelial carcinoma (UC) that have progressed after chemotherapy. Furthermore, combination therapy with ICIs and chemotherapy or radiation therapy has shown promise in treating bladder cancer. While there are challenges associated with ICIs, including adverse effects, immune-related adverse events, and lack of efficacy in some patients, they remain a promising option for bladder cancer treatment, especially in cases where other treatment options have failed. This review paper focuses on the current role, challenges, and future trends of immunotherapy in the management of bladder cancer.
Analysis of coexisting pathogens in nasopharyngeal swabs from COVID-19

Background The impact of COVID-19 on the world is still ongoing, and it is currently under regular management. Although most infected people have flu-like symptoms and can cure themselves, coexisting pathogens in COVID-19 patients should not be taken lightly. The present study sought to investigate the coexisting pathogens in SARS-CoV-2 infected patients and identify the variety and abundance of dangerous microbes to guide treatment strategies with a better understanding of the untested factors. Methods We extracted total DNA and RNA in COVID-19 patient specimens from nasopharyngeal swabs to construct a metagenomic library and utilize Next Generation Sequencing (NGS) to discover chief bacteria, fungi, and viruses in the body of patients. High-throughput sequencing data from Illumina Hiseq 4000 were analyzed using Krona taxonomic methodology for species diversity. Results We studied 56 samples to detect SARS-CoV-2 and other pathogens and analyzed the species diversity and community composition of these samples after sequencing. Our results showed some threatening pathogens such as Mycoplasma pneumoniae, Klebsiella pneumoniae, Streptococcus pneumoniae, and some previously reported pathogens. SARS-CoV-2 combined with bacterial infection is more common. The results of heat map analysis showed that the abundance of bacteria was mostly more than 1000 and that of viruses was generally less than 500. The pathogens most likely to cause SARS-CoV-2 coinfection or superinfection include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Klebsiella pneumoniae, and Human gammaherpesvirus 4. Conclusions The current coinfection and superinfection status is not optimistic. Bacteria are the major threat group that increases the risk of complications and death in COVID-19 patients and attention should be paid to the use and control of antibiotics. Our study investigated the main types of respiratory pathogens prone to coexisting or superinfection in COVID-19 patients, which is valuable for identifying and treating SARS-CoV-2.
Wedge resection—finding its place in early-stage non-small cell lung cancer?

respectively, as radiologic criteria for wedge resection. Other features seen on HRCT, specifically spicules of margin, lobulated shape, and vascular passage were also associated with greater rates of recurrence. Together, these data support the benefit of wedge resection for stage IA NSCLC in this cohort. Perhaps more important is how we are to interpret these data amidst the ever-evolving landscape of thoracic surgery. Within the past year, two landmark, prospective, randomized trials have been performed demonstrating the non-inferiority of sublobar resection for NSCLC with nodule size of 2 cm or less. The Japan Clinical Oncology Group (JCOG) 0802 demonstrated segmentectomy as non-inferior to lobectomy, with outstanding recurrence-free survival and overall survival (6). This was followed by Cancer and Leukemia Group B (CALGB) 140503 which corroborated the results of non-inferiority in a western population, in this case grouping both wedge resections and segmentectomies together in a sublobar cohort (11). Theoretic advantages of sublobar resections include preservation of lung parenchyma and lower perioperative
An integrative view on the systematic position of the cupressophyte Cephalotaxus

Abstract We made an in‐depth review of historical studies of the cupressophyte conifer genus Cephalotaxus Siebold & Zucc. with an emphasis on its systematic position. We suggest that the systematic position of the genus is better understood using an integrative approach, so the evolution of phenetic characters is discussed within the context of recent phylogenomics. We propose that the genus should be classified as a separate family Cephalotaxaceae belonging to the clade consisting of Cupressaceae, Cephalotaxaceae, and Taxaceae; the family Cephalotaxaceae is sister to the Taxaceae but not nested within the Taxaceae and is characterized by a unique set of characters including morphology, anatomy, embryology, and chemistry. The family Cephalotaxaceae shows transitional characters between the Cupressaceae and the Taxaceae; the family possesses female cones with a primary cone axis bearing 5–8 pairs of decussate bracts, which is similar to the typical female cones of the Cupressaceae, on the one hand, and may have given rise to the reduced female cone of the Taxaceae with one terminal ovule partially or completely enclosed in a fleshy aril. In parallel, the compound male cone of the Cephalotaxaceae evolved into the seemingly “simple” male cones of the Taxaceae by means of reduction, elimination, and fusion.
Computational evaluation of bioactive compounds in Curcuma zanthorrhiza targeting SIRT1 and NFκB

Type 2 diabetes mellitus (T2DM) is a metabolic disease with a high risk of complications and mortality. Novel T2DM therapeutic interventions are needed to combat this disease. This study aimed to identify pathways involved in T2DM and investigate sesquiterpenoid compounds from Curcuma zanthorrhiza that could act as SIRT1 activators and NFκB inhibitors. Protein–protein interaction and bioactive compound analysis were conducted using the STRING and STITCH databases, respectively. Molecular docking was used to determine the compounds’ interactions with SIRT1 and NFκB, while toxicity prediction was performed using Protox II. The results showed that curcumin could act as a SIRT1 activator (4I5I, 4ZZJ, and 5BTR) and NFκB inhibitor on the p52 relB complex and p50–p65 heterodimer, while xanthorrhizol could function as an IκK inhibitor. The toxicity prediction indicated that the active compounds of C. zanthorrhiza were relatively nontoxic because beta-curcumene, curcumin, and xanthorrizol belong to toxicity classes 4 or 5. These findings suggest that the bioactive compounds of C. zanthorrhiza could be promising candidates for developing SIRT1 activators and NFκB inhibitors to combat T2DM.
Clinical analysis and medium-term follow-up of simultaneous interventional therapy for compound congenital heart disease in children: a single-center retrospective study

Objective This study aimed to explore the safety and efficacy of simultaneous interventional therapy for compound congenital heart disease (CCHD) in children. Methods In total, 155 children with CCHD who received simultaneous interventional therapy at the Children's Hospital of Chongqing Medical University between January 2007 and December 2021 were included in study. Data on clinical manifestations, transthoracic echocardiography, electrocardiogram, and follow-up were retrospectively analyzed. Results The most common type of CCHD was atrial septal defect (ASD) combined with ventricular septal defect (VSD), accounting for 32.3% of the patients. Simultaneous interventional therapy was successfully administered to 151 children (97.4%). The pulmonary gradient of patients with pulmonary stenosis decreased from 47.3 ± 21.9 mmHg to 15.2 ± 12.2 mmHg (P < 0.05) immediately after the procedure. One patient had failed PBPV as he had residual PS >40 mmHg post procedure. The right ventricular dimension and left ventricular end-diastolic dimension significantly decreased in the first month after the procedure in patients with ASD combined with VSD. Twenty-five (16.1%) patients had mild residual shunt, which spontaneously disappeared in more than half of these patients 6 months after the procedure. The major adverse events were minimal (n = 4, 2.58%), including one patient requiring drug treatment for complete atrioventricular block and three patients receiving surgical treatment because of cardiac erosion, anterior tricuspid valve chordae rupture, and hemolysis, respectively. Conclusions ASD combined with VSD is the most common type of CCHD in children, and simultaneous interventional therapy for CCHD in children is safe and effective with satisfactory results. Ventricular remodeling can be reversed in patients with ASD combined with VSD 1 month after the procedure. Most adverse events associated with interventional therapy are mild and manageable.
Ruminococcus gnavus bacteraemia showing morphological diversity on Gram staining: a case report and literature review

Ruminococcus gnavus , a Gram-positive anaerobic coccus, is a common constituent of the human gut microbiota but rarely causes any disease in humans. Herein, we report a case of R. gnavus bacteraemia in an immunocompromised 73-year-old man with sigmoid colon perforation. R. gnavus is usually reported as Gram-positive diplococci or short chains on Gram staining; however, in our patient, a blood isolate showed Gram-positive cocci in long chains, and organisms from an anaerobic subculture showed morphological diversity. This case provides insight into the morphological diversity of R. gnavus , which might help with the recognition of these bacteria in the preliminary identification stage on Gram staining.
Flavonoid glycoside fraction of Ginkgo biloba extract modulates antioxidants imbalance in vanadium-induced brain damage

Human and animal diseases have always been reported to be treated by medicinal herbs owing to their constituents. Excess sodium metavanadate is a potential environmental toxin when consumed and could induce oxidative damage leading to various neurological disorders and Parkinsons-like diseases. This study is designed to investigate the impact of the flavonoid Glycoside Fraction of Ginkgo Biloba Extract (GBE) (at 30 mg/kg body weight) on vanadium-treated rats. Animals were divided randomly into four groups: Control (Ctrl, normal saline), Ginkgo Biloba (GIBI, 30mg/kg BWT), Vanadium (VANA, 10 mg/kg BWT) and Vanadium + Ginkgo biloba (VANA + GIBI). Markers of oxidative stress (Glutathione Peroxidase and Catalase) were assessed and found to be statistically increased with GIBI when compared with CTRL and treatment groups. Results from routine staining revealed that the control and GIBI group had a normal distribution of cells and a pronounced increase in cell count respectively compared to the VANA group. When compared to the VANA group, the NeuN photomicrographs revealed that the levels of GIBI were within the normal range (***p < 0.001; ** p < 001). The treatment with GIBI showed a better response by increasing the neuronal cells in the VANA+GIBI when compared with the VANA group. The NLRP3 Inflammasome photomicrographs denoted that there was a decrease in NLRP3-positive cells in the control and GIBI groups. The treatment group shows fewer cells compared to that of the VANA group. The treatment group shows fewer cells compared to that of the VANA group. The findings of the study confirmed that ginkgo biloba extract via its flavonoid glycoside fraction has favorable impacts in modulating vanadium-induced brain damage with the potential ability to lower antioxidant levels and reduce neuroinflammation.
Topology-aware Serverless Function-Execution Scheduling

Cloud-edge serverless applications or serverless deployments spanning multiple regions introduce the need to govern the scheduling of functions to satisfy their functional constraints or avoid performance degradation. For instance, functions may require to be allocated to specific private (edge) nodes that have access to specialised resources or to nodes with low latency to access a certain database to decrease the overall latency of the application. State-of-the-art serverless platforms do not support directly the implementation of topological constraints on the scheduling of functions. We address this problem by presenting a declarative language for defining topology-aware, function-specific serverless scheduling policies, called tAPP. Given a tAPP script, a compatible serverless scheduler can enforce different, co-existing topological constraints without requiring ad-hoc platform deployments. We prove our approach feasible by implementing a tAPP-based serverless platform as an extension of the Apache OpenWhisk serverless platform. We show that, compared to vanilla OpenWhisk, our extension does not negatively impact the performance of generic, non-topology-bound serverless scenarios, while it increases the performance of topology-bound ones.
Toward a paradigm shift in feedback research: Five further steps influenced by self-regulated learning theory

Abstract As the articles in this special issue on “Psychological Perspectives on the Effects and Effectiveness of Assessment Feedback” have shown, feedback is a key factor in education. Although there exists a substantial body of research on the topic, it is imperative to continue advancing the field. My aim is to outline five steps to solidify the potential paradigm shift that the feedback field may already be experiencing, while incorporating the insights gleaned from the articles within this special issue. Firstly, there is a need to develop new models that thoroughly explore and operationalize the intricacies of the feedback phenomenon. Secondly, it is essential to conceptualize feedback as a dynamic process and collect data that directly investigates this process. Thirdly, it would be advantageous to leverage insights from the self-regulated learning field, which has made significant strides in advancing measurement methods applicable to feedback research. Fourthly, employing multimodal methods can enrich our comprehension of the multifaceted nature of the feedback process. Lastly, placing the feedback agent at the core of the feedback process, with particular attention to individual differences, is of utmost importance.
Personalization of politicians on Instagram: what Generation Z wants to see in political posts

ABSTRACT While research has examined how politicians engage in personalized presentations of themselves and their policies, and how journalists personalize political coverage, few studies have asked voters what types of personalization they wish to see from politicians. In-depth interviews with Generation Z, who heavily use Instagram, identify visual and verbal elements of politicians’ Instagram posts that they consider influential on their beliefs and actions. Responses reveal several elements, including two that expand the contours of what constitutes persuasive political personalization. Successful personalization includes politicians participating in two-way conversations with followers and adopting a backstage pass aesthetic when showing what politicians do on the job and how they feel about it. Both tactics can make politicians seem credible and personally relatable, which is the foundation for effective electronic word-of-mouth communication.
Differentiating Occult Neuroretinitis and Non-Arteritic Anterior Ischaemic Optic Neuropathy: Clinical and Optical Coherence Tomography Characteristics

ABSTRACT We report clinical and optical coherence tomography (OCT) differences among patients with occult neuroretinitis and non-arteritic anterior ischaemic optic neuropathy (NAAION). We retrospectively reviewed records of patients with a final diagnosis of occult neuroretinitis and NAAION seen at our institute. Data were collected regarding patient demographics, clinical features, concomitant systemic risk factors, visual function, and optical coherence tomography (OCT) findings at presentation and subsequent follow-up. Fourteen and 16 patients were diagnosed to have occult neuroretinitis and NAAION, respectively. Patients with NAAION were slightly older (median age 49, inter-quartile range [IQR]: 45–54 years, versus 41, IQR: 31–50 years) than patients with neuroretinitis. Seventy-five per cent of patients with NAAION were male versus 43% with neuroretinitis (p = 0.07). Systemic risk factors were present in 87.5% of patients with NAAION versus 21.4% in patients with neuroretinitis (p = 0.001). At presentation, all patients presented with blurred vision, had similar visual function, and had optic disc oedema. In addition, none of the patients had evident retinitis lesions, but 10 (71%) showed evident retinitis lesion at follow-up. Neuroretinitis patients had more often vitreous cells (64% versus 6%, p = 0.001), and subretinal fluid (78.6% versus 37.5%, p = 0.03) than the patients with NAAION. In summary, NAAION patients tended to be slightly older, more often male, and had associated systemic diseases more often than those with neuroretinitis. Neuroretinitis patients more often had posterior vitreous cells and subretinal fluid on OCT. However, larger prospective studies are needed.
Reasons for customizing packaged enterprise systems: a case study on an enterprise asset management system

ABSTRACT Companies acquire information systems as software products developed by software vendors. These products, usually referred to as packaged enterprise systems (PESs), are customized to fit a customer company’s business needs and processes. Despite its practical relevance, the literature discusses customization sporadically and primarily focuses on the implementation, adoption, and critical success factors of enterprise resource planning systems. Another type of PES, enterprise asset management (EAM), is even more greatly overlooked, although it has a very large user base and a significant market share. In this paper, we explore why PESs are customized. We conduct a case study on the customization of a commercial EAM system in the Nordic region, which involves interviewing 16 business representatives and consultants involved in implementing and operating the EAM system in their respective organizations. We describe four categories of reasons for customizing EAM: the product lacks some features, business process needs necessitate customization, project management issues, and the relationship between the consultants and the business units leads to customization. We also show when they emerge in relation to the EAM project’s phases. Identifying and understanding these reasons can help product vendors and their customers assign their resources appropriately and tailor their activities toward achieving efficiency and feasibility
ent-Verticilide B1 inhibits type 2 ryanodine receptor channels and is antiarrhythmic in Casq2-/- mice.

Ca2+ leak from cardiac ryanodine receptor (RyR2) is an established mechanism of sudden cardiac death (SCD), whereby dysregulated Ca2+ handling causes ventricular arrhythmias. We previously discovered the RyR2-selective inhibitor ent-(+)-verticilide (ent-1), a 24-membered cyclooligomeric depsipeptide that is the enantiomeric form of a natural product (nat-(-)-verticilide). Here, we examined its 18-membered ring-size oligomer (ent-verticilide B1; ent-B1) in single RyR2 channel assays, [3H]ryanodine binding assays, and in Casq2-/- cardiomyocytes and mice, a gene-targeted model of SCD. ent-B1 inhibited RyR2 single-channels and [3H]ryanodine binding with low micromolar potency, and RyR2-mediated spontaneous Ca2+ release in Casq2-/- cardiomyocytes with sub-micromolar potency. ent-B1 was a partial RyR2 inhibitor, with maximal inhibitory efficacy of less than 50%. ent-B1 was stable in plasma, with a peak plasma concentration of 1460 ng/ml at 10 min and half-life of 45 min after intraperitoneal administration of 3 mg/kg in mice. Both 3 mg/kg and 30 mg/kg ent-B1 significantly reduced catecholamine-induced ventricular arrhythmia in Casq2-/- mice. Hence, we have identified a novel chemical entity, ent-B1, that preserves the mechanism of action of a hit compound and shows therapeutic efficacy. These findings strengthen RyR2 as an antiarrhythmic drug target and highlight the potential of investigating the mirror-image isomers of natural products to discover new therapeutics. Significance Statement The cardiac ryanodine receptor (RyR2) is an untapped target in the stagnant field of antiarrhythmic drug development. We have confirmed RyR2 as an antiarrhythmic target in a mouse model of sudden cardiac death and shown the therapeutic efficacy of a second enantiomeric natural product.
A digital twin for DNA data storage based on comprehensive quantification of errors and biases

Archiving data in synthetic DNA offers unprecedented storage density and longevity. Handling and storage introduce errors and biases into DNA-based storage systems, necessitating the use of Error Correction Coding (ECC) which comes at the cost of added redundancy. However, insufficient data on these errors and biases, as well as a lack of modelling tools, limit data-driven ECC development and experimental design. In this study, we present a comprehensive characterisation of the error sources and biases present in the most common DNA data storage workflows, including commercial DNA synthesis, PCR, decay by accelerated aging, and sequencing-by-synthesis. Using the data from 40 sequencing experiments, we build a digital twin of the DNA data storage process, capable of simulating state-of-the-art workflows and reproducing their experimental results. We showcase the digital twin’s ability to replace experiments and rationalize the design of redundancy in two case studies, highlighting opportunities for tangible cost savings and data-driven ECC development.