Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients. Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response. Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits. Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.
Neonates in the Intensive Care Unit: Maternal Health-Related Quality of Life and Depression After Term and Preterm Births

Background/Objective: To examine maternal physical and mental health-related quality of life (HRQoL) and depression after early and late preterm and term births in the early postpartum period. Method: In a prospective pilot study, three groups of women whose newborns had to be treated in the neonatal ward during the immediate postpartum period were established and compared with each other: 20 women with extremely to very preterm birth, 20 with moderate to late preterm birth and 20 women with term birth. All participants completed the Short Form-12 Health Survey (SF-12) to measure HRQoL, and the Edinburgh Postnatal Depression Scale (EPDS) to detect depressive symptoms combined with independently developed questions to evaluate anxiety and psychological distress. Results: Maternal psychological HRQoL was significantly worse in the very preterm birth group compared to moderate to late preterm birth (p < 0.001) and full-term birth groups (p = 0.004). There were no differences between the birth groups in depressive symptoms (p = 0.083), anxiety (p = 0.238), perceived stress (p = 0.340) and the general psychological distress values (p = 0.755). In the EPDS, the depression screening instrument 30 to 65% were beyond the cut-off-value to detect major depression. Conclusions: During the early postpartum period, an extensive medical care focussing on acute stress, HRQoL parameters and depression may be a good step to improving maternal well-being.
Prediction and Modeling of Neuropsychological Scores in Alzheimer’s Disease Using Multimodal Neuroimaging Data and Artificial Neural Networks

Background: In recent years, predicting and modeling the progression of Alzheimer’s disease (AD) based on neuropsychological tests has become increasingly appealing in AD research. Objective: In this study, we aimed to predict the neuropsychological scores and investigate the non-linear progression trend of the cognitive declines based on multimodal neuroimaging data. Methods: We utilized unimodal/bimodal neuroimaging measures and a non-linear regression method (based on artificial neural networks) to predict the neuropsychological scores in a large number of subjects (n = 1143), including healthy controls (HC) and patients with mild cognitive impairment non-converter (MCI-NC), mild cognitive impairment converter (MCI-C), and AD. We predicted two neuropsychological scores, i.e., the clinical dementia rating sum of boxes (CDRSB) and Alzheimer’s disease assessment scale cognitive 13 (ADAS13), based on structural magnetic resonance imaging (sMRI) and positron emission tomography (PET) biomarkers. Results: Our results revealed that volumes of the entorhinal cortex and hippocampus and the average fluorodeoxyglucose (FDG)-PET of the angular gyrus, temporal gyrus, and posterior cingulate outperform other neuroimaging features in predicting ADAS13 and CDRSB scores. Compared to a unimodal approach, our results showed that a bimodal approach of integrating the top two neuroimaging features (i.e., the entorhinal volume and the average FDG of the angular gyrus, temporal gyrus, and posterior cingulate) increased the prediction performance of ADAS13 and CDRSB scores in the converting and stable stages of MCI and AD. Finally, a non-linear AD progression trend was modeled to describe the cognitive decline based on neuroimaging biomarkers in different stages of AD. Conclusion: Findings in this study show an association between neuropsychological scores and sMRI and FDG-PET biomarkers from normal aging to severe AD.
Self-Regulation of Slippery Deadlines: The Role of Procrastination in Work Performance

We investigated the causes and impact of procrastination on “slippery deadlines,” where the due date is ill-defined and can be autonomously extended, using the unique applied setting of grievance arbitration across two studies. In Study One, using 3 years of observed performance data derived from Canadian arbitration cases and a survey of leading arbitrators, we examined the effect of individual differences, self-regulatory skills, workloads and task characteristics on time delay. Observed delay here is a critical criterion, where justice is emphasized to be swift and sure. Multilevel Modeling established trait procrastination as a substantive predictor of observed delay, equivalent to the environmental contributors of expediting the arbitration procedure or grievance complexity. Also, despite substantive negative consequence of delay for both arbitrators and their clients, arbitrators who scored one standard deviation above the mean in procrastination took approximately 83 days to write their decisions compared to the 26 days for arbitrators one standard deviation below the mean. In Study Two, we conducted a replication and extension survey with a much larger group of American arbitrators. Consistent with Temporal Motivation Theory (TMT), trait procrastination was largely explained by expectancy, value, and sensitivity to time related traits and skills, which together accounted for majority of the variance in trait procrastination, leaving little left for other explanations. For example, perfectionism connection to procrastination appears to be distal, being largely mediated by each of TMT’s core variables. Finally, procrastination was largely synonymous with a deadline pacing style, indicating that observed delay can be used as a proxy for procrastination as long as little or no prior work was done (e.g., a u-shaped pacing style is not synonymous). In all, our results indicate that procrastination is rampant in the workplace and has seriously detrimental effects.
Clinical Symptoms and Outcomes of Severe Pneumonia Caused by Chlamydia psittaci in Southwest China

Here, we aimed to retrospectively analyze the clinical characteristics of 27 patients with severe pneumonia caused by Chlamydia psittaci between January 2019 and April 2021 in southwest China. To this end, we collected data on the exposure history, clinical symptoms, laboratory examination, imaging characteristics, evolution, etiology, treatment, and outcomes to suggest a better diagnosis and prevention system. Our results showed that a metagenomic next-generation sequencing test could provide early diagnosis. All patients were sensitive to quinolones and tetracyclines, and the recovery rate was relatively high. Overall, all patients were in critical condition with moderate to severe acute respiratory distress syndrome and shock. In conclusion, early diagnosis of pneumonia caused by C. psittaci depends on effective molecular testing, and most patients recover after treatment.
Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage

Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) represent an attractive resource for cardiac regeneration. However, survival and functional integration of transplanted iPS-CM is poor and remains a major challenge for the development of effective therapies. We hypothesized that paracrine effects of co-transplanted mesenchymal stromal cells (MSCs) augment the retention and therapeutic efficacy of iPS-CM in a mouse model of myocardial infarction (MI). To test this, either iPS-CM, MSC, or both cell types were transplanted into the cryoinfarction border zone of syngeneic mice immediately after injury. Bioluminescence imaging (BLI) of iPS-CM did not confirm enhanced retention by co-application of MSC during the 28-day follow-up period. However, histological analyses of hearts 28 days after cell transplantation showed that MSC increased the fraction of animals with detectable iPS-CM by 2-fold. Cardiac MRI analyses showed that from day 14 after transplantation on, the animals that have received cells had a significantly higher left ventricular ejection fraction (LVEF) compared to the placebo group. There was no statistically significant difference in LVEF between animals transplanted only with iPS-CM or only with MSC. However, combined iPS-CM and MSC transplantation resulted in higher LVEF compared to transplantation of single-cell populations during the whole observation period. Histological analyses revealed that MSC increased the capillarization in the myocardium when transplanted alone or with iPS-CM and decreased the infarct scar area only when transplanted in combination with iPS-CM. These results indicate that co-transplantation of iPS-CM and MSC improves cardiac regeneration after cardiac damage, demonstrating the potential of combining multiple cell types for increasing the efficacy of future cardiac cell therapies.
Oral Prevotella Species and Their Connection to Events of Clinical Relevance in Gastrointestinal and Respiratory Tracts

Prevotella is recognized as one of the core anaerobic genera in the oral microbiome. In addition, members of this genus belong to microbial communities of the gastrointestinal and respiratory tracts. Several novel Prevotella species, most of them of oral origin, have been described, but limited knowledge is still available of their clinical relevance. Prevotella melaninogenica is among the anaerobic commensals on oral mucosae from early months of life onward, and other early colonizing Prevotella species in the oral cavity include Prevotella nigrescens and Prevotella pallens. Oral Prevotella species get constant access to the gastrointestinal tract via saliva swallowing and to lower airways via microaspiration. At these extra-oral sites, they play a role as commensals but also as potentially harmful agents on mucosal surfaces. The aim of this narrative review is to give an updated overview on the involvement of oral Prevotella species in gastrointestinal and respiratory health and disease.
Critical Role of Astrocytic Polyamine and GABA Metabolism in Epileptogenesis

Accumulating evidence indicate that astrocytes are essential players of the excitatory and inhibitory signaling during normal and epileptiform activity via uptake and release of gliotransmitters, ions, and other substances. Polyamines can be regarded as gliotransmitters since they are almost exclusively stored in astrocytes and can be released by various mechanisms. The polyamine putrescine (PUT) is utilized to synthesize GABA, which can also be released from astrocytes and provide tonic inhibition on neurons. The polyamine spermine (SPM), synthesized form PUT through spermidine (SPD), is known to unblock astrocytic Cx43 gap junction channels and therefore facilitate astrocytic synchronization. In addition, SPM released from astrocytes may also modulate neuronal NMDA, AMPA, and kainate receptors. As a consequence, astrocytic polyamines possess the capability to significantly modulate epileptiform activity. In this study, we investigated different steps in polyamine metabolism and coupled GABA release to assess their potential to control seizure generation and maintenance in two different epilepsy models: the low-[Mg2+] model of temporal lobe epilepsy in vitro and in the WAG/Rij rat model of absence epilepsy in vivo. We show that SPM is a gliotransmitter that is released from astrocytes and significantly contributes to network excitation. Importantly, we found that inhibition of SPD synthesis completely prevented seizure generation in WAG/Rij rats. We hypothesize that this antiepileptic effect is attributed to the subsequent enhancement of PUT to GABA conversion in astrocytes, leading to GABA release through GAT-2/3 transporters. This interpretation is supported by the observation that antiepileptic potential of the Food and Drug Administration (FDA)-approved drug levetiracetam can be diminished by specifically blocking astrocytic GAT-2/3 with SNAP-5114, suggesting that levetiracetam exerts its effect by increasing surface expression of GAT-2/3. Our findings conclusively suggest that the major pathway through which astrocytic polyamines contribute to epileptiform activity is the production of GABA. Modulation of astrocytic polyamine levels, therefore, may serve for a more effective antiepileptic drug development in the future.
Admission Lower Serum Phosphate Ion Levels Predict Acute Hydrocephalus of Aneurysmal Subarachnoid Hemorrhage

Introduction: The relationship between serum phosphate ion (sPi) and the occurrence of acute hydrocephalus (aHCP) in aneurysmal subarachnoid hemorrhage (aSAH) remains largely unknown and controversial. The primary aim of this study was to investigate the association between sPi on admission and aHCP following aSAH. Methods: The study included 635 patients over the age of 19 years diagnosed with aSAH in our institution from September 2012 to June 2018. Data on clinical characteristics, laboratory parameters, treatments, and outcomes were collected and analyzed. The association between lower sPi levels and aHCP was assessed in univariate and multivariate analyses. Propensity-score matching (PSM) analysis was performed to reduce significant differences in baseline characteristics between the aHCP group and non-HCP group. Results: The overall incidence of aHCP following aSAH was 19.37% (123/512). Lower sPi levels were detected in patients with aHCP compared with those without [0.86 (0.67–1.06) vs. 1.04 (0.84–1.21) mmol/L] in the univariate analysis. In the multivariate analysis, lower sPi level, high modified Fisher (mFisher) grade, and high Hunt-Hess grade were associated with aHCP [odds ratios (OR) 1.729, 95% confidence interval (CI) 1.139–2.623, p = 0.01; mFisher OR 0.097,95% CI 0.055–0.172, p < 0.001; Hunt-Hess, OR 0.555, 95% CI 0.320–0.961, P = 0.036]. After PSM, the matched aHCP group had a significantly lower sPi level than the matched non-aHCP group [0.86 (0.67–1.06) vs. 0.94 (0.76–1.12) mmol/L, p = 0.044]. The area under the curve (AUC) of the sPi level and the logistic regression model based on these predictors (sPi, Hunt-Hess grade, and mFisher grade) was 0.667 and 0.840 (sensitivity of 88.6% and specificity of 68.4%) for predicting aHCP, respectively. Conclusions: Lower sPi levels predict the occurrence of aHCP, and the model constructed by sPi levels, Hunt-Hess grade, and mFisher grade markedly enhances the prediction of aHCP after aSAH.
Stimulation of angiogenesis through collagen gel by applying shear stress and interstitial flow

The induction of angiogenesis has been documented in many diseases such as cancer, arthritis, and diabetes. Angiogenesis can be stimulated by a variety of signals including a mechanical stress applied to the apical side of endothelial cells. To get a better understanding of this mechanical stimulus, a parallel plate flow chamber was designed and tested to elicit a constant laminar flow onto a monolayer of endothelial cells. The goal of this research was to develop a more physiologically similar in vitro system to study the effects of shear stress on endothelial cells. Unlike prior flow chamber apparatus, this chamber allows the cells to be seeded on collagen gel rather than a rigid substrate to more closely mimic in vivo environment. A shear stress of I Pa was applied to the endothelial cells for a duration of 36 hours. Results show that after flow was initiated for this duration, a change in shape of the endothelial cells can be seen when compared to the static condition. Elongation and alignment of cells plated on collagen gel can be seen in the direction of flow, though not at pronounced as the elongation typically seen from cells plated on rigid substrates. Nuclear and F-actin staining also revealed similar results. The nuclear staining revealed a confluent monolayer formation occurred prior to flow and was maintained throughout the experiment. A change in organization of the F-actin fibers, from radially protruding out from the nucleus during static condition to a more ordered arrangement after the flow was implemented could also be seen. The changes in cell appearance illustrates that the mechanical stimulus of a shear stress has an effect on endothelial cell arrangement and suggests that this effect depends to some degree on the cell adhesion substrate stiffness. Furthermore, new research in this area can look at both the signaling that leads to these morphological changes as well as the factors that control angiogenesis. Thesis Supervisor: Roger Kamm Title: Professor of Mechanical Engineering
PTRF/Cavin-1 as a Novel RNA-Binding Protein Expedites the NF-κB/PD-L1 Axis by Stabilizing lncRNA NEAT1, Contributing to Tumorigenesis and Immune Evasion in Glioblastoma

Background Immunotherapy, especially checkpoint inhibitors targeting PD-1 or PD-L1, has revolutionized cancer therapy. However, PD-1/PD-L1 inhibitors have not been investigated thoroughly in glioblastoma (GBM). Studies have shown that polymerase 1 and transcript release factor (PTRF/Cavin-1) has an immune-suppressive function in GBM. Thus, the relationship between PTRF and PD-L1 and their role in immune suppression requires further investigation in GBM. Methods We used public databases and bioinformatics analysis to investigate the relationship between PTRF and PD-L1. We next confirmed the predicted relationship between PTRF and PD-L1 in primary GBM cell lines by using different experimental approaches. RIP-Seq, RIP, ChIP, and qRT-PCR were conducted to explore the molecular mechanism of PTRF in immunosuppression. Results We found that PTRF stabilizes lncRNA NEAT1 to induce NF-κB and PD-L1 and promotes immune evasion in GBM. PTRF was found to correlate with immunosuppression in the public GBM databases. PTRF increased the level of PD-L1 in primary cell lines from GBM patients. We carried out RIP-Seq of GBM cells and found that PTRF interacts with lncRNA NEAT1 and stabilizes its mRNA. PTRF also promoted the activity of NF-κB by suppressing UBXN1 expression via NEAT1 and enhanced the transcription of PD-L1 through NF-κB activation. Finally, PTRF promoted immune evasion in GBM cells by regulating PD-1 binding and PD-L1 mediated T cell cytotoxicity. Conclusions In summary, our study identified the PTRF-NEAT1-PD-L1 axis as a novel immune therapeutic target in GBM.
Impact of Asymmetric Weight Update on Neural Network Training With Tiki-Taka Algorithm

Recent progress in novel non-volatile memory-based synaptic device technologies and their feasibility for matrix-vector multiplication (MVM) has ignited active research on implementing analog neural network training accelerators with resistive crosspoint arrays. While significant performance boost as well as area- and power-efficiency is theoretically predicted, the realization of such analog accelerators is largely limited by non-ideal switching characteristics of crosspoint elements. One of the most performance-limiting non-idealities is the conductance update asymmetry which is known to distort the actual weight change values away from the calculation by error back-propagation and, therefore, significantly deteriorates the neural network training performance. To address this issue by an algorithmic remedy, Tiki-Taka algorithm was proposed and shown to be effective for neural network training with asymmetric devices. However, a systematic analysis to reveal the required asymmetry specification to guarantee the neural network performance has been unexplored. Here, we quantitatively analyze the impact of update asymmetry on the neural network training performance when trained with Tiki-Taka algorithm by exploring the space of asymmetry and hyper-parameters and measuring the classification accuracy. We discover that the update asymmetry level of the auxiliary array affects the way the optimizer takes the importance of previous gradients, whereas that of main array affects the frequency of accepting those gradients. We propose a novel calibration method to find the optimal operating point in terms of device and network parameters. By searching over the hyper-parameter space of Tiki-Taka algorithm using interpolation and Gaussian filtering, we find the optimal hyper-parameters efficiently and reveal the optimal range of asymmetry, namely the asymmetry specification. Finally, we show that the analysis and calibration method be applicable to spiking neural networks.
The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma

Background MAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response. Methods Six metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation. Results Compared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment. Conclusions MAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.