Miracle-dz/UniFAR-FTUs huggingface dataset:
Surgery offers survival advantage over radiotherapy in patients who are 80 years and older with Stage I and II NSCLC: A retrospective cohort study of 7,045 patients

Objective Elderly people are less likely than younger patients to undergo curative surgery for early-stage lung cancer because of the greater risk of surgery and postoperative complications. We investigated the relationship between treatment modality and the risk of all-cause and lung cancer-specific mortality to compare the efficacy of surgical treatment with radiotherapy in patients with stage I and II non-small cell lung cancer (NSCLC) who were ≥80 years old. Methods We extracted data from the most recent Surveillance, Epidemiology, and End Results 9 registry study database (2010–2017). We mainly selected patients with stage I and II NSCLC who were ≥80 years old, and after screening, 7,045 cases were selected for our study. We used univariate analysis, stratified analysis, and multiple regression equation analysis to examine all-cause mortality and lung cancer-specific mortality in different treatment modalities. The overall and stratified populations' survival curves were plotted using the Kaplan–Meier method. The competing risk regression method of Fine and Gray was used to estimate mortality specific to lung cancer. Results In the fully adjusted model, all-cause mortality was 1.97 times higher in the radiotherapy-only group (hazard ration (HR) = 1.97, 95% confidence interval (CI) = 1.81–2.14, p < 0.0001) than in the surgery-only group. The lung cancer-specific mortality rate was 1.22 times higher in the radiotherapy-only group (HR = 1.22, 95% CI = 1.13–1.32, p < 0.0001) than in the surgery-only group. The median overall survival (OS) in the surgery-only, radiation therapy-only, surgery plus radiation therapy, and no-treatment groups were 58 months, 31 months, 36 months, and 10 months, respectively. Median lung cancer-specific survival was 61 months, 32 months, 38 months, and 11 months, respectively. The surgery-only group had the highest 1-year OS (0.8679,95% CI = 0.8537–0.8824) and 5-year OS (0.4873, 95% CI = 0.4632–0.5126). Conclusions Surgery had a higher overall and lung cancer-specific survival rate than radiotherapy and no treatment in the elderly early-stage NSCLC population. For patients with stage I and stage II NSCLC at advanced ages, surgical treatment might have a greater potential survival benefit.
How personal values and critical dispositions support digital citizenship development in higher education students

The virtual environment’s expansion and role in young people’s lives accentuate the need for developing transversal competences such as digital citizenship. The process may be supported by personal resources like personal values and critical thinking dispositions. With this study on 536 young students’ students aged 18 to 26 (M = 20.85, SD = 1.60), we analysed the relationship between two adjacent personal values, universalism and self-direction, and students’ digital citizenship. Moreover, we examined the role of critical thinking dispositions, namely learning orientation, and cognitive integrity in supporting digital citizenship development. Following structural equation modelling (SEM) analyses, the results show that universalism and learning orientation significantly positively influence digital citizenship, whereas cognitive integrity has a negative effect. Further, personal values positively associate with critical thinking dispositions.
The prognostic impact of the immune signature in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that retain their poor prognosis despite recent advances in their standard of care. As the involvement of the immune system against HNSCC development is well-recognized, characterization of the immune signature and the complex interplay between HNSCC and the immune system could lead to the identification of novel therapeutic targets that are required now more than ever. In this study, we investigated RNA sequencing data of 530 HNSCC patients from The Cancer Genome Atlas (TCGA) for which the immune composition (CIBERSORT) was defined by the relative fractions of 10 immune-cell types and expression data of 45 immune checkpoint ligands were quantified. This initial investigation was followed by immunohistochemical (IHC) staining for a curated selection of immune cell types and checkpoint ligands markers in tissue samples of 50 advanced stage HNSCC patients. The outcome of both analyses was correlated with clinicopathological parameters and patient overall survival. Our results indicated that HNSCC tumors are in close contact with both cytotoxic and immunosuppressive immune cells. TCGA data showed prognostic relevance of dendritic cells, M2 macrophages and neutrophils, while IHC analysis associated T cells and natural killer cells with better/worse prognostic outcome. HNSCC tumors in our TCGA cohort showed differential RNA over- and underexpression of 28 immune inhibitory and activating checkpoint ligands compared to healthy tissue. Of these, CD73, CD276 and CD155 gene expression were negative prognostic factors, while CD40L, CEACAM1 and Gal-9 expression were associated with significantly better outcomes. Our IHC analyses confirmed the relevance of CD155 and CD276 protein expression, and in addition PD-L1 expression, as independent negative prognostic factors, while HLA-E overexpression was associated with better outcomes. Lastly, the co-presence of both (i) CD155 positive cells with intratumoral NK cells; and (ii) PD-L1 expression with regulatory T cell infiltration may hold prognostic value for these cohorts. Based on our data, we propose that CD155 and CD276 are promising novel targets for HNSCC, possibly in combination with the current standard of care or novel immunotherapies to come.
Atlas of human dental pulp cells at multiple spatial and temporal levels based on single-cell sequencing analysis

The dental pulp plays a crucial role in the long-term maintenance of tooth function. The progress of endodontic treatment and pulp tissue regeneration engineering has made pulp-regeneration therapy promising in clinical practice. However, the mechanisms of pulp regeneration and the role of dental stem cells in development and regeneration have not been fully elucidated. Bridging the gaps between clinical operation and basic research is urgently needed. With the application of single-cell sequencing technology in dental research, the landscapes of human dental pulp cells have begun being outlined. However, the specific cellular heterogeneity of dental pulp cells, especially that of dental stem cells, at different spatial and temporal levels, is still unclear. In this study, we used single-cell RNA sequencing analysis of pulp samples at four different developmental stages and combined the findings with immunohistochemical staining to explore the development of dental pulp and stem cells. The results revealed temporal changes in the proportion of pulp cells during development. For example, mononuclear phagocytes accounted for a higher proportion in early samples. Odontoblasts identified by DMP1 had a higher expression of ion channel-related and neurodevelopment-related genes. Subpopulations were identified in fibroblasts, odontoblasts, and mesenchymal stem cells. We identified a subclass of odontoblasts that expresses DGKI and RRBP1 present in early developmental samples. A population of earlier mesenchymal stem cells expressed the SEPTIN gene, which may have greater proliferative and differentiation potential. Furthermore, dental pulp stem cells can differentiate into two directions: mineralization and myogenesis. In summary, the specific cellular heterogeneity of dental pulp cells was revealed at different spatial and temporal levels. These findings may shed light on the mechanism of tooth development. The gene expression profile of developing pulp cells may help to select cells for regenerative engineering and improve the success of dental pulp regeneration.
Engineered red blood cells (activating antigen carriers) drive potent T cell responses and tumor regression in mice

Activation of T cell responses is essential for effective tumor clearance; however, inducing targeted, potent antigen presentation to stimulate T cell responses remains challenging. We generated Activating Antigen Carriers (AACs) by engineering red blood cells (RBCs) to encapsulate relevant tumor antigens and the adjuvant polyinosinic-polycytidylic acid (poly I:C), for use as a tumor-specific cancer vaccine. The processing method and conditions used to create the AACs promote phosphatidylserine exposure on RBCs and thus harness the natural process of aged RBC clearance to enable targeting of the AACs to endogenous professional antigen presenting cells (APCs) without the use of chemicals or viral vectors. AAC uptake, antigen processing, and presentation by APCs drive antigen-specific activation of T cells, both in mouse in vivo and human in vitro systems, promoting polyfunctionality of CD8+ T cells and, in a tumor model, driving high levels of antigen-specific CD8+ T cell infiltration and tumor killing. The efficacy of AAC therapy was further enhanced by combination with the chemotherapeutic agent Cisplatin. In summary, these findings support AACs as a potential vector-free immunotherapy strategy to enable potent antigen presentation and T cell stimulation by endogenous APCs with broad therapeutic potential.
GALAXY GROWTH BY MERGING IN THE NEARBY UNIVERSE

We measure the mass growth rate by merging for a wide range of galaxy types. We present the small-scale (0.014 h−170 Mpc < r < 11 h70−1 Mpc) projected cross-correlation functions w(rp) of galaxy subsamples from the spectroscopic sample of the NYU Value-Added Galaxy Catalog (5 × 105 galaxies of redshifts 0.03 < z < 0.15) with galaxy subsamples from the Sloan Digital Sky Survey imaging (4 × 107 galaxies). We use smooth fits to de-project the two-dimensional functions w(rp) to obtain smooth three-dimensional real-space cross-correlation functions ξ(r) for each of several spectroscopic subsamples with each of several imaging subsamples. Because close pairs are expected to merge, the three-space functions and dynamical evolution time estimates provide galaxy accretion rates. We find that the accretion onto massive blue galaxies and onto red galaxies is dominated by red companions, and that onto small-mass blue galaxies, red and blue galaxies make comparable contributions. We integrate over all types of companions and find that at fixed stellar mass, the total fractional accretion rates onto red galaxies (∼3 h70 percent per Gyr) are greater than that onto blue galaxies (∼1 h70 percent per Gyr). These rates are almost certainly overestimates because we have assumed that all close pairs merge as quickly as the merger time that we used. One conclusion of this work is that if the total growth of red galaxies from z = 1 to z = 0 is mainly due to merging, the merger rates must have been higher in the past.
Deconstructing delirium in the post anaesthesia care unit

The course of neuro-cognitive recovery following anaesthesia and surgery is distinctive and poorly understood. Our objective was to identify patterns of neuro-cognitive recovery of the domains routinely assessed for delirium diagnosis in the post anaesthesia care unit (PACU) and to compare them to the cognitive recovery patterns observed in other studies; thereby aiding in the identification of pathological (high risk) patterns of recovery in the PACU. We also compared which of the currently available tests (3D-CAM, CAM-ICU, and NuDESC) is the best to use in PACU. This was a post hoc secondary analysis of data from the Alpha Max study which involved 200 patients aged over 60 years, scheduled for elective surgery under general anaesthesia lasting more than 2 h. These patients were assessed for delirium at 30 min following arrival in the PACU, if they were adequately arousable (Richmond Agitation Sedation Score ≥ −2). All tests for delirium diagnosis (3D-CAM, CAM-ICU, and NuDESC) and the sub-domains assessed were compared to understand temporal recovery of neurocognitive domains. These data were also analysed to determine the best predictor of PACU delirium. We found the incidence of PACU delirium was 35% (3D-CAM). Individual cognitive domains were affected differently. Few individuals had vigilance deficits (6.5%, n = 10 CAM-ICU) or disorganized thinking (19% CAM-ICU, 27.5% 3D-CAM), in contrast attention deficits were common (72%, n = 144) and most of these patients (89.5%, n = 129) were not sedated (RASS ≥ −2). CAM-ICU (27%) and NuDESC (52.8%) detected fewer cases of PACU delirium compared to 3D-CAM. In conclusion, return of neurocognitive function is a stepwise process; Vigilance and Disorganized Thinking are the earliest cognitive functions to return to baseline and lingering deficits in these domains could indicate an abnormal cognitive recovery. Attention deficits are relatively common at 30 min in the PACU even in individuals who appear to be awake. The 3D CAM is a robust test to check for delirium in the PACU.
Theoretical exploration on structures, bonding aspects and molecular docking of α-aminophosphonate ligated copper complexes against SARS-CoV-2 proteases

Recent years have witnessed a growing interest in the biological activity of metal complexes of α-aminophosphonates. Here for the first time, a detailed DFT study on five α-aminophosphonate ligated mononuclear/dinuclear CuII complexes is reported using the dispersion corrected density functional (B3LYP-D2) method. The electronic structures spin densities, FMO analysis, energetic description of spin states, and theoretical reactivity behaviour using molecular electrostatic potential (MEP) maps of all five species are reported. All possible spin states of the dinuclear species were computed and their ground state S values were determined along with the computation of their magnetic coupling constants. NBO analysis was also performed to provide details on stabilization energies. A molecular docking study was performed for the five complexes against two SARS-CoV-2 coronavirus protein targets (PDB ID: 6LU7 and 7T9K). The docking results indicated that the mononuclear species had a higher binding affinity for the targets compared to the dinuclear species. Among the species investigated, species I showed the highest binding affinity with the SARS-CoV-2 Omicron protease. NPA charge analysis showed that the heteroatoms of model species III had a more nucleophilic nature. A comparative study was performed to observe any variations and/or correlations in properties among all species.
Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism

A common consequence of chronic renal disease is secondary hyperparathyroidism (SHPT) and is closely related to the mortality and morbidity of uremia patients. Secondary hyperparathyroidism (SHPT) is caused by excessive PTH production and release, as well as parathyroid enlargement. At present, the mechanism of cell proliferation in secondary hyperparathyroidism (SHPT) is not completely clear. Decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), and 1,25(OH)2D3 insufficiency all lead to a decrease in cell proliferation suppression, and activation of multiple pathways is also involved in cell proliferation in renal hyperparathyroidism. The interaction between the parathormone (PTH) and parathyroid hyperplasia and 1,25(OH)2D3 has received considerable attention. 1,25(OH)2D3 is commonly applied in the therapy of renal hyperparathyroidism. It regulates the production of parathormone (PTH) and parathyroid cell proliferation through transcription and post-transcription mechanisms. This article reviews the role of 1,25(OH)2D3 in parathyroid cells in secondary hyperparathyroidism and its current understanding and potential molecular mechanism.
Corresponding anatomical of the macaque superior parietal lobule areas 5 (PE) subdivision reveal similar connectivity patterns with humans

Using the animal brain as a cross-species tool for human brain research based on imaging features can provide more potential to reveal comprehensive human brain analysis. Previous studies have shown that human Brodmann area 5 (BA5) and macaque PE are homologous regions. They are both involved in processes depth and direction information during the touch process in the arm movement. However, recent studies show that both BA5 and PE are not homogeneous. According to the cytoarchitecture, BA5 is subdivided into three different subregions, and PE can be subdivided into PEl, PEla, and PEm. The species homologous relationship among the subregions is not clear between BA5 and PE. At the same time, the subdivision of PE based on the anatomical connection of white matter fiber bundles needs more verification. This research subdivided the PE of macaques based on the anatomical connection of white matter fiber bundles. Two PE subregions are defined based on probabilistic fiber tracking, one on the anterior side and the other on the dorsal side. Finally, the research draws connectivity fingerprints with predefined homologous target areas for the BA5 and PE subregions to reveal the characteristics of structure and functions and gives the homologous correspondence identified.
Hypericin, a potential new BH3 mimetic

Many types of cancer such as prostate cancer, myeloid leukemia, breast cancer, glioblastoma display strong chemo resistance, which is supported by enhanced expression of multiple anti-apoptotic Bcl-2, Bcl-XL and Mcl-1 proteins. The viable anti-cancer strategies are based on developing anti-apoptotic Bcl-2 proteins inhibitors, BH3 mimetics. Our focus in past years has been on the investigating a new potential BH3 mimetic, Hypericin (Hyp). Hyp is a naturally occurring photosensitive compound used in photodynamic therapy and diagnosis. We have demonstrated that Hyp can cause substantial effects in cellular ultrastructure, mitochondria function and metabolism, and distribution of Bcl2 proteins in malignant and non-malignant cells. One of the possible mechanisms of Hyp action could be the direct interactions between Bcl-2 proteins and Hyp. We investigated this assumption by in silico computer modelling and in vitro fluorescent spectroscopy experiments with the small Bcl2 peptide segments designed to correspond to Bcl2 BH3 and BH1 domains. We show here that Hyp interacts with BH3 and BH1 peptides in concentration dependent manner, and shows the stronger interactions than known BH3 mimetics, Gossypol (Goss) and ABT-263. In addition, interactions of Hyp, Goss and ABT263, with whole purified proteins Bcl-2 and Mcl-1 by fluorescence spectroscopy show that Hyp interacts stronger with the Bcl-2 and less with Mcl-1 protein than Goss or ABT-263. This suggest that Hyp is comparable to other BH3 mimetics and could be explore as such. Hyp cytotoxicity was low in human U87 MG glioma, similar to that of ABT263, where Goss exerted sufficient cytotoxicity, suggesting that Hyp acts primarily on Bcl-2, but not on Mcl-1 protein. In combination therapy, low doses of Hyp with Goss effectively decreased U87 MG viability, suggesting a possible synergy effect. Overall, we can conclude that Hyp as BH3 mimetic acts primarily on Bcl-2 protein and can be explored to target cells with Bcl-2 over-expression, or in combination with other BH3 mimetics, that target Mcl-1 or Bcl-XL proteins, in dual therapy.
Comparison between 10 and 12 mg doses of intrathecal hyperbaric (0.5%) bupivacaine on sensory block level after first spinal failure in cesarean section: A double-blind, randomized clinical trial

Background Reducing adverse effects during cesarean delivery and improving the quality of sensory blocks with appropriate doses of intrathecal hyperbaric bupivacaine can play an important role in the safe management of cesarean delivery. The aim of this study was to compare the doses of 10 and 12 mg of intrathecal hyperbaric bupivacaine 0.5% on sensory block level after first spinal failure in cesarean section (CS). Methods In this double-blind, randomized clinical trial, 40 candidates of CS after first spinal failure with class I-II based on American Society of Anesthesiologists (ASA) were randomly assigned into two equal groups (n = 20). Group A and B received the spinal anesthesia with 10 mg and 12 mg of hyperbaric bupivacaine (0.5%), respectively. Maximum levels of sensory block, motor block quality, and vital signs were measured in two groups by 60 min after SPA. Incidence of SPA complications during surgery were also recorded. Data were analyzed by SPSS ver.21 software using repeated measures analysis of variance at 95% confidence interval (CI) level. Results Excellent quality of sensory blocks and complete quality of motor blocks were achieved in all participants (100%). However, the mean time to onset of anesthesia (4.47 ± 0.69 vs. 3.38 ± 0.47, P < 0.001) and time to reach T10 level (60.73 ± 11.92 vs. 79.00 ± 19.21, P < 0.001) in the Group A, were significantly shorter than in the patients of Group B. The incidence of hypotension (P = 0.001), nausea/vomiting (P = 0.007) and bradycardia (P = 0.012) as well as administration of ephedrine and atropine were significantly higher in Group B compared to Group A. Conclusion Spinal anesthesia can be safely repeated with a 10 mg of hyperbaric bupivacaine 0.5% in a caesarean section after the initial spinal failure. Clinical trial registration [https://en.irct. ir/trial/40714], identifier [IRCT20120915010841N20].
A deep 96-well plate RBC storage platform for high-throughput screening of novel storage solutions

Background: Red blood cell (RBC) storage solutions, also known as additive solutions (ASs), first developed in the 1970s, enable extended storage of RBCs. Unfortunately, the advancements in this field have been limited, due to labor intensive and time-consuming serial in vitro and in vivo testing, coupled with very high commercialization hurdles. This study examines the utility of deep 96-well plates for preliminary screenings of novel ASs through comparison of RBC storage with the standard PVC bags in terms of hemolysis and ATP levels, under both normoxic (N) and hypoxic/hypocapnic (H) storage conditions. The necessity for the presence of DEHP, normally provided by PVC bags, is also examined. Materials and methods: A pool of 2 ABO compatible RBC units was split between a bag and a plate. Each plate well contained either 1, 2 or 0 PVC strips cut from standard storage bags to supply DEHP. The H bags and plates were processed in an anaerobic glovebox and stored in O2 barrier bags. Hemolysis and ATP were measured bi-weekly using standard methods. Results: Final ATP and hemolysis values for the plate-stored RBCs were comparable to the typical values observed for 6-week storage of leukoreduced AS-3 RBCs in PVC bags under both N and H conditions. Hemolysis was below FDA and EU benchmarks of 1% and 0.8%, respectively, and excluding DEHP from plates during storage, resulted in an inconsequential increase when compared to bag samples. Discussion: In combination with high-throughput metabolomics workflow, this platform provides a highly efficient preliminary screening platform to accelerate the initial testing and consequent development of novel RBC ASs.