Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of EP Chemotherapy Followed by IP Chemotherapy Combined with Radiotherapy in the Treatment of Extensive-Stage Small-Cell Lung Cancer.

PURPOSE To explore the efficacy and safety of etoposide + cisplatin (EP) and irinotecan + cisplatin (IP) sequential chemotherapy combined with radiotherapy in the treatment of extensive-stage small-cell lung cancer (SCLC). METHODS A total of 108 patients with extensive-stage SCLC were divided into the EP+IP group (n=54, sequential IP chemotherapy), and the EP group (n=54, EP chemotherapy). The changes in the level of serum tumor markers and the number of circulating tumor cells (CTCs) in the peripheral blood were compared between the two groups of patients before and after treatment. The patients were followed up to record the survival status and tumor progression. RESULTS The overall effective rate for bone metastases in the EP+IP group was significantly higher than that in the EP group. The EP+IP group displayed significantly lower levels of serum VEGF, Ki-67 and peripheral blood CTCs than the EP group. In addition, the follow-up results manifested that the median overall survival (OS) in the EP+IP group and the EP group were 16.2 months and 12.7 months, respectively, and the median progression-free survival (PFS) was 8.4 months and 5.9 months, respectively. The 2-year OS was 13.0% and 7.4%, respectively. Furthermore, the log-rank test illustrated that the OS and PFS in the EP+IP group were significantly superior to those in the EP group. CONCLUSIONS EP and IP sequential chemotherapy combined with radiotherapy is more effective than EP chemotherapy combined with radiotherapy in the treatment of extensive-stage SCLC. The former can markedly reduce the levels of serum tumor markers and peripheral blood CTCs, increase the long-term survival of patients and reduce the occurrence of blood-related adverse reactions.
Model of a Device-Level Combined Wireless Network Based on NB-IoT and IEEE 802.15.4 Standards for Low-Power Applications in a Diverse IoT Framework

With the development of the Internet of Things (IoT), Low Data Rate-Personal Area Networks (LR-WPAN) have been deployed for different applications. Now comes the need to integrate these networks in search of greater connectivity, performances, and geographic coverage. This integration is facilitated by the recent deployment of low power wide area networks (LPWAN) in the licensed bands, especially narrowband IoT (NB-IoT) and long-term evolution for machine-type communications (LTE-M), which are standardized technologies that will continue evolving as part of the fifth generation (5G) specifications. This paper proposes a design methodology for combined networks using LR-WPAN and LPWAN technologies. These networks are combined at the device level using a cluster-tree topology. An example is shown here, where an existing IEEE 802.15. 4 network is combined with NB-IoT. To this end, new dual nodes are incorporated, acting as cluster heads. The paper discusses the different aspects of formation and operation of the combined network. A dynamic link selection (DLS) algorithm is also proposed, based on which cluster headers dynamically determine the preferred link, depending on link quality and type of traffic. Extensive simulations show that the DLS algorithm significantly increases battery life on dual nodes, which are the nodes with the highest power demands.
Ecological Role of Volatile Organic Compounds Emitted by Pantoea agglomerans as Interspecies and Interkingdom Signals

Volatile organic compounds (VOCs) play an essential role in microbe–microbe and plant–microbe interactions. We investigated the interaction between two plant growth-promoting rhizobacteria, and their interaction with tomato plants. VOCs produced by Pantoea agglomerans MVC 21 modulates the release of siderophores, the solubilisation of phosphate and potassium by Pseudomonas (Ps.) putida MVC 17. Moreover, VOCs produced by P. agglomerans MVC 21 increased lateral root density (LRD), root and shoot dry weight of tomato seedlings. Among the VOCs released by P. agglomerans MVC 21, only dimethyl disulfide (DMDS) showed effects similar to P. agglomerans MVC 21 VOCs. Because of the effects on plants and bacterial cells, we investigated how P. agglomerans MVC 21 VOCs might influence bacteria–plant interaction. Noteworthy, VOCs produced by P. agglomerans MVC 21 boosted the ability of Ps. putida MVC 17 to increase LRD and root dry weight of tomato seedlings. These results could be explained by the positive effect of DMDS and P. agglomerans MVC 21 VOCs on acid 3-indoleacetic production in Ps. putida MVC 17. Overall, our results clearly indicated that P. agglomerans MVC 21 is able to establish a beneficial interaction with Ps. putida MVC 17 and tomato plants through the emission of DMDS.
Cellulose-based scaffolds enhance pseudoislets formation and functionality

In vitro research for the study of type 2 diabetes (T2D) is frequently limited by the availability of a functional model for islets of Langerhans. To overcome the limitations of obtaining pancreatic islets from different sources, such as animal models or human donors, immortalized cell lines as the insulin-producing INS1E β-cells have appeared as a valid alternative to model insulin-related diseases. However, immortalized cell lines are mainly used in flat surfaces or monolayer distributions, not resembling the spheroid-like architecture of the pancreatic islets. To generate islet-like structures, the use of scaffolds appeared as a valid tool to promote cell aggregations. Traditionally-used hydrogel encapsulation methods do not accomplish all the requisites for pancreatic tissue engineering, as its poor nutrient and oxygen diffusion induces cell death. Here, we use cryogelation technology to develop a more resemblance scaffold with the mechanical and physical properties needed to engineer pancreatic tissue. This study shows that carboxymethyl cellulose (CMC) cryogels prompted cells to generate β-cell clusters in comparison to gelatin-based scaffolds, that did not induce this cell organization. Moreover, the high porosity achieved with CMC cryogels allowed us to create specific range pseudoislets. Pseudoislets formed within CMC-scaffolds showed cell viability for up to 7 d and a better response to glucose over conventional monolayer cultures. Overall, our results demonstrate that CMC-scaffolds can be used to control the organization and function of insulin-producing β-cells, representing a suitable technique to generate β-cell clusters to study pancreatic islet function.
Transvaginal Ultrasound-Guided Core Biopsy—Experiences in a Comprehensive Cancer Centre

Simple Summary Adequate histological diagnosis defines the treatment in gynaecologic oncology. Although transvaginal ultrasound (TVUS) has widespread use in the diagnosis of pelvic tumours, TVUS-guided core biopsy is not a common procedure. In this study we summarize our experience in TVUS-guided biopsies performed in a comprehensive cancer centre, discussing the results of 303 patients who underwent this procedure. In addition, we compare the histological results of the biopsies with subsequent surgical histological results in 94 cases. Our study demonstrates that TVUS-guided core biopsy is a safe and effective histological sampling procedure providing adequate tissue for pathological evaluation in 99% of cases. Compared to surgically obtained histology, this procedure can reliably guide therapy, as its performance is satisfactory. In our opinion, TVUS-guided core biopsy is an effective diagnostic method providing possible benefits to patients referred for suspicion of gynaecological malignancy. Abstract In this paper, we report our experience of transvaginal ultrasound (TVUS)-guided core biopsies involving 303 patients referred to the gynaecological ultrasound unit of our national comprehensive cancer centre. Adequate histologic specimens were obtained in 299 patients (98.7%). The most common sites of biopsy sampling were the adnexa (29.7%), the vaginal stump or wall (13.5%), the uterus (11.6%) and the peritoneum (10.2%). Malignancy was confirmed in two-thirds of patients (201/303) and a primary malignancy was diagnosed in 111 of the 201 histologically verified malignant cases (55.2%). Interestingly, 23.9% (48/201) of malignant tumours were proven to have a non-gynaecological origin. Among them, gastrointestinal tumours occurred the most frequently (31/48 patients). Three abscesses were discovered following the biopsy procedure, resulting in a complication rate of 1%. In 94 (31%) patients, subsequent surgery allowed the comparison of the ultrasound-guided and surgically obtained histologic results. We found inaccuracy in 12 cases (12.8%), which is discussed in this paper in detail. Sensitivity, specificity, PPV and NPV to diagnose malignancy was 94.8%, 94.1%, 98.7% and 80.0%, respectively. This is the largest study reported to date about the efficacy and safety of TVUS-guided core biopsy in evaluating pelvic lesions giving rise to a suspicion of gynaecological cancer.
Screening the Presence of Non-Typhoidal Salmonella in Different Animal Systems and the Assessment of Antimicrobial Resistance

Simple Summary In this study, for the first time in Chile, we compared resistance profiles of Salmonella strains isolated from 4047 samples from domestic and wild animals. A total of 106 Salmonella strains (2.61%) were isolated, and their serogroups were characterized and tested for susceptibility to 16 different antimicrobials. This study reports 47 antimicrobial-resistant (AMR) Salmonella strains (44.3% of total strains). Of the 47, 28 corresponded to single-drug resistance (26.4%) and 19 to multidrug resistance (17.9%). The association between AMR and a subset of independent variables was evaluated using multivariate logistic models. Interestingly, S. Enteritidis was highly persistent in animal production systems; however, we report that serogroup D strains were 18 times less likely to be resistant to at least one antimicrobial agent than the most common serogroup (serogroup B). The antimicrobials presenting the greatest contributions to AMR were ampicillin, streptomycin and tetracycline. Abstract Salmonella is a major bacterial foodborne pathogen that causes the majority of worldwide food-related outbreaks and hospitalizations. Salmonellosis outbreaks can be caused by multidrug-resistant (MDR) strains, emphasizing the importance of maintaining public health and safer food production. Nevertheless, the drivers of MDR Salmonella serovars have remained poorly understood. In this study, we compare the resistance profiles of Salmonella strains isolated from 4047 samples from domestic and wild animals in Chile. A total of 106 Salmonella strains (2.61%) are isolated, and their serogroups are characterized and tested for susceptibility to 16 different antimicrobials. The association between antimicrobial resistance (AMR) and a subset of independent variables is evaluated using multivariate logistic models. Our results show that 47 antimicrobial-resistant strains were found (44.3% of the total strains). Of the 47, 28 correspond to single-drug resistance (SDR = 26.4%) and 19 are MDR (17.9%). S. Enteritidis is highly persistent in animal production systems; however, we report that serogroup D strains are 18 times less likely to be resistant to at least one antimicrobial agent than the most common serogroup (serogroup B). The antimicrobials presenting the greatest contributions to AMR are ampicillin, streptomycin and tetracycline. Additionally, equines and industrial swine are more likely to acquire Salmonella strains with AMR. This study reports antimicrobial-susceptible and resistant Salmonella in Chile by expanding the extant literature on the potential variables affecting antimicrobial-resistant Salmonella.
Event-Based Prospective Memory Deficit in Children with ADHD: Underlying Cognitive Factors and Association with Symptoms

Event-based prospective memory (PM) was investigated in children with Attention deficit/hyperactivity disorder (ADHD), using a novel experimental procedure to evaluate the role of working memory (WM) load, attentional focus, and reward sensitivity. The study included 24 children with ADHD and 23 typically-developing controls. The experimental paradigm comprised one baseline condition (BC), only including an ongoing task, and four PM conditions, varying for targets: 1 Target (1T), 4 Targets (4T), Unfocal (UN), and Reward (RE). Children with ADHD were slower than controls on all PM tasks and less accurate on both ongoing and PM tasks on the 4T and UN conditions. Within the ADHD group, the accuracy in the RE condition did not differ from BC. A significant relationship between ADHD-related symptoms and reduced accuracy/higher speed in PM conditions (PM and ongoing trials), but not in BC, was detected. Our data provide insight on the adverse role of WM load and attentional focus and the positive influence of reward in the PM performance of children with ADHD. Moreover, the relation between PM and ADHD symptoms paves the road for PM as a promising neuropsychological marker for ADHD diagnosis and intervention.
PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation

(1) Background: Niraparib and Talazoparib are poly (ADP-ribose) polymerase (PARP) 1/2 inhibitors. It is assumed that combining PARP inhibitors with radiotherapy could be beneficial for cancer treatment. In this study, melanoma cells were treated with Niraparib and Talazoparib in combination with ionizing radiation (IR). (2) Methods: The effects of Talazoparib and Niraparib in combination with IR on cell death, clonogenicity and cell cycle arrest were studied in healthy primary fibroblasts and primary melanoma cells. (3) Results: The melanoma cells had a higher PARP1 and PARP2 content than the healthy fibroblasts, and further increased their PARP2 content after the combination therapy. PARP inhibitors both sensitized fibroblasts and melanoma cells to IR. A clear supra-additive effect of KI+IR treatment was detected in two melanoma cell lines analyzing the surviving fraction. The cell death rate increased in the healthy fibroblasts, but to a larger extent in melanoma cells after combined treatment. Finally, a lower percentage of cells in the radiosensitive G2/M phase is present in the healthy fibroblasts compared to the melanoma cells. (4) Conclusions: Both PARP inhibitors sensitize melanoma cells to IR. Healthy tissue seems to be less affected than melanoma cells. However, the great heterogeneity of the results suggests prior testing of the tumor cells in order to personalize the treatment.
Advances in the Pathogenesis of EBV-Associated Diffuse Large B Cell Lymphoma

Simple Summary The last World Health Organization classification of Tumours of Haematopoietic and Lymphoid Tissues defines a new category, EBV + DLBCL, NOS, which incidence varies among different populations. Given the oncogenic characteristics of both latent and lytic viral proteins, EBV could replace some of the cellular pathways and/or mutations observed in non EBV-associated cases. In addition, the virus may turn the tumor microenvironment in a tolerogenic, in order to promote tumorigenesis, and may have also influence on survival in specific populations. The analysis of EBV pathogenesis in DLBCL may exhibit new potential targets for DLBCL treatment. Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma (NHL) in adults. Epstein–Barr virus (EBV) positive DLBCL of the elderly was defined by the World Health Organization (WHO) in 2008, it was restricted only to patients older than 50 years old, and it was attributed to immunesenescence associated with physiological aging. After the description of EBV-associated DLBCL in children and young adults, the WHO redefined the definition, leading to the substitution of the modifier “elderly” with “not otherwise specified” (EBV + DLBCL, NOS) in the updated classification, and it is no more considered provisional. The incidence of EBV + DLBCL, NOS varies around the world, in particular influenced by the percentage of EBV+ cells used as cut-off to define a case as EBV-associated. EBV has effect on the genetic composition of tumor cells, on survival, and at the recruitment of immune cells at the microenvironment. In this review, the role of EBV in the pathogenesis of DLBCL is discussed.
Symptom Cluster-Matching Antidepressant Treatment: A Case Series Pilot Study

Despite treating depression with antidepressants, their effectiveness is often insufficient. Comparative effectiveness studies and meta-analyses show the effectiveness of antidepressants; however, they do not provide clear indications as to the choice of a specific antidepressant. The rational choice of antidepressants may be based on matching their mechanisms of action to the symptomatic profiles of depression, reflecting the heterogeneity of symptoms in different patients. The authors presented a series of cases of patients diagnosed with depression in whom at least one previous antidepressant treatment was shown to be ineffective before drug targeted symptom cluster-matching treatment (SCMT). The presented pilot study shows for the first time the effectiveness of SCMT in the different clusters of depressive symptoms. All the described patients obtained recovery from depressive symptoms after introducing drug-targeted SCMT. Once validated in clinical trials, SCMT might become an effective and rational method of selecting an antidepressant according to the individual profile of depressive symptoms, the mechanism of their formation, and the mechanism of drug action. Although the study results are preliminary, SCMT can be a way to personalize treatment, increasing the likelihood of improvement even in patients who meet criteria for treatment-resistant depression.
Mesenchymal Stem Cell-Derived Exosomes Ameliorate Alzheimer’s Disease Pathology and Improve Cognitive Deficits

The accumulation of extracellular β-amyloid (Aβ) plaques within the brain is unique to Alzheimer’s disease (AD) and thought to induce synaptic deficits and neuronal loss. Optimal therapies should tackle the core AD pathophysiology and prevent the decline in memory and cognitive functions. This study aimed to evaluate the therapeutic performance of mesenchymal stem cell-derived exosomes (MSC-exosomes), which are secreted membranous elements encapsulating a variety of MSC factors, on AD. A human neural cell culture model with familial AD (FAD) mutations was established and co-cultured with purified MSC-exosomes. 2-[18F]Fluoro-2-deoxy-d-glucose ([18F]FDG) and novel object recognition (NOR) testing were performed before/after treatment to evaluate the therapeutic effect in vivo. The AD-related pathology and the expression of neuronal memory/synaptic plasticity-related genes were also evaluated. The results showed that MSC-exosomes reduced Aβ expression and restored the expression of neuronal memory/synaptic plasticity-related genes in the cell model. [18F]FDG-PET imaging and cognitive assessment revealed a significant improvement in brain glucose metabolism and cognitive function in AD transgenic mice. The phase of neurons and astrocytes in the brain of AD mice were also found to be regulated after treatment with MSC-exosomes. Our study demonstrates the therapeutic mechanism of MSC-exosomes and provides an alternative therapeutic strategy based on cell-free MSC-exosomes for the treatment of AD.
The stabilization of yes‐associated protein by TGFβ‐activated kinase 1 regulates the self‐renewal and oncogenesis of gastric cancer stem cells

Gastric cancer (GC) is the most frequent digestive system malignant tumour and the second most common cause of cancer death globally. Cancer stem cell (CSC) is a small percentage of cancer cells in solid tumours that have differentiation, self‐renewal and tumorigenic capabilities. They have an active participation in the initiation, development, metastasis, recurrence and resistance of tumours to chemotherapy and radiotherapy. Gastric cancer stem cells (GCSCs) have been shown to be correlated with GC initiation and metastasis. In this study, we found that TAK1 expression level in GC tissues was significantly increased compared to the adjacent non‐cancerous tissues by RT‐qPCR, Western blot and immunohistochemistry. TAK1 has been identified as a critical molecule that promoted a variety of malignant GC phenotypes both in vivo and in vitro and promoted the self‐renewal of GCSCs. Mechanistically, TAK1 was up‐regulated by IL‐6 and prevented the degradation of yes‐associated protein (YAP) in the cytoplasm by binding to YAP. Thus, TAK1 promoted the SOX2 and SOX9 transcription and the self‐renewal and oncogenesis of GCSCs. Our findings provide insights into the mechanism of self‐renewal and tumorigenesis of TAK1 in GCSCs and have broad implications for clinical therapies.
Effect of Multishell Diffusion MRI Acquisition Strategy and Parcellation Scale on Rich-Club Organization of Human Brain Structural Networks

The majority of network studies of human brain structural connectivity are based on single-shell diffusion-weighted imaging (DWI) data. Recent advances in imaging hardware and software capabilities have made it possible to acquire multishell (b-values) high-quality data required for better characterization of white-matter crossing-fiber microstructures. The purpose of this study was to investigate the extent to which brain structural organization and network topology are affected by the choice of diffusion magnetic resonance imaging (MRI) acquisition strategy and parcellation scale. We performed graph-theoretical network analysis using DWI data from 35 Human Connectome Project subjects. Our study compared four single-shell (b = 1000, 3000, 5000, 10,000 s/mm2) and multishell sampling schemes and six parcellation scales (68, 200, 400, 600, 800, 1000 nodes) using five graph metrics, including small-worldness, clustering coefficient, characteristic path length, modularity and global efficiency. Rich-club analysis was also performed to explore the rich-club organization of brain structural networks. Our results showed that the parcellation scale and imaging protocol have significant effects on the network attributes, with the parcellation scale having a substantially larger effect. Regardless of the parcellation scale, the brain structural networks exhibited a rich-club organization with similar cortical distributions across the parcellation scales involving at least 400 nodes. Compared to single b-value diffusion acquisitions, the deterministic tractography using multishell diffusion imaging data consisting of shells with b-values higher than 5000 s/mm2 resulted in significantly improved fiber-tracking results at the locations where fiber bundles cross each other. Brain structural networks constructed using the multishell acquisition scheme including high b-values also exhibited significantly shorter characteristic path lengths, higher global efficiency and lower modularity. Our results showed that both parcellation scale and sampling protocol can significantly impact the rich-club organization of brain structural networks. Therefore, caution should be taken concerning the reproducibility of connectivity results with regard to the parcellation scale and sampling scheme.