Prognostic and therapeutic implications of iron-related cell death pathways in acute myeloid leukemia

Acute myeloid leukemia (AML) is a blood cancer that is diverse in terms of its molecular abnormalities and clinical outcomes. Iron homeostasis and cell death pathways play crucial roles in cancer pathogenesis, including AML. The objective of this study was to examine the clinical significance of genes involved in iron-related cell death and apoptotic pathways in AML, with the intention of providing insights that could have prognostic implications and facilitate the development of targeted therapeutic interventions. Gene expression profiles, clinical information, and molecular alterations were integrated from multiple datasets, including TCGA-LAML and GSE71014. Our analysis identified specific molecular subtypes of acute myeloid leukemia (AML) displaying varying outcomes, patterns of immune cell infiltration, and profiles of drug sensitivity for targeted therapies based on the expression of genes involved in iron-related apoptotic and cell death pathways. We further developed a risk model based on four genes, which demonstrated promising prognostic value in both the training and validation cohorts, indicating the potential of this model for clinical decision-making and risk stratification in AML. Subsequently, Western blot analysis showed that the expression levels of C-Myc and CyclinD1 were significantly reduced after CD4 expression levels were knocked down. The findings underscore the potential of iron-related cell death pathways as prognostic biomarkers and therapeutic targets in AML, paving the way for further research aimed at understanding the molecular mechanisms underlying the correlation between iron balance, apoptosis regulation, and immune modulation in the bone marrow microenvironment

Effectiveness and safety of osimertinib in patients with metastatic EGFR T790M-positive NSCLC: An observational real-world study.

Osimertinib showed encouraging efficacy in patients with advanced EGFR T790M-positive NSCLC in previous randomized controlled trials. This real-world study aimed to evaluate the effectiveness and safety of osimertinib in a real-world setting. This observational study (NCT03133234) included 74 patients with metastatic EGFR T790M-positive NSCLC who progressed on prior EGFR TKI therapy and received osimertinib between May 2016 and April 2018 at the Kiang Wu Hospital in Macau. Response rate (RR) and other endpoints (progression-free survival [PFS], overall survival [OS], disease control rate [DCR], stable disease rate, and adverse events) were assessed. Survival data were estimated using the Kaplan-Meier method. All patients had stage IV lung adenocarcinoma and 25.6% had brain metastases; median age was 58 years (range 28-84 years) and 83.8% of patients had received at least three prior lines of treatment. The median duration of osimertinib treatment was 8 months (range, 1-25 months). RR and DCR were 67.5% (95% CI 56.9-78.1) and 79.8% (95% CI 70.7-88.9), respectively, while 12.1% had stable disease. The median PFS was 9.0 months (95% CI 6.7-11.2 months), and the median OS was 12.0 months (95% CI 8.8-15.1 months). Nausea (25.8%) and decreased appetite (20.2%) were the most common adverse events associated with osimertinib treatment. Even though most patients had at least three lines of prior treatment, real-world RR and PFS with osimertinib in this study were consistent with those from randomized controlled trials; no new safety signals were observed

Social Behavioral Sensing: An Exploratory Study to Assess Learning Motivation and Perceived Relatedness of University Students using Mobile Sensing

Learning motivation plays a crucial role in student’s daily study life since it greatly affects academic performance and engagement. Perceived relatedness, based on self-determined theory, is an important predictor of learning motivation. Today, assessment for both of them still relies on subjective evaluations and self-reports, which is time-consuming and onerous. Hence, we propose a novel approach blended with mobile sensing by simultaneously collecting psychological measurements and objective mobile sensing data from N=58 undergraduates to explore new methods of assessing learning motivation and perceived relatedness. We identify a variety of social behavioral patterns from mobile sensing data, and investigate associations between psychological measures and these patterns. Our study helps enlighten what the new forms of assessing learning motivation and perceived relatedness in education could be, and paves the way for personalizing intervention in future research

Characteristics and survival of primary urothelial carcinoma of the prostate: A multi-center retrospective study of 18 cases

Objectives: To explore the features, treatment, and outcomes of primary urothelial carcinoma of the prostate (PUCP) in a multicenter study. Methods: The clinical and imaging features, pathological findings, treatment, and outcomes of patients diagnosed with PUCP from January 2011 to April 2022 at three institutions were collected and analyzed. The Kaplan–Meier method and log-rank test were used to assess survival rates of the overall group and survival differences between groups according to TNM stage. Results: The study cohort comprised 18 patients with PUCP of mean age 72.4±7.8 years. Dysuria and urinary frequency were the most common symptoms (77.8 %). Sixteen (88.9 %) patients had normal serum total PSA concentrations. Most patients showed abnormalities on urinalysis. MRI was the most accurate diagnostic imaging method (88.9 %). As to immunohistochemistry findings, GATA-3 (81.8 %) and P63 (84.6 %) were positive in most examined patients; however, no lesions were positive for PSA. Three (17.6 %) patients with T1N0M0 and T2N0M0 tumors underwent radical cystectomy. Eleven (64.7 %) patients which almost all had T4 tumors received systematic therapy, most of them receiving chemotherapy with gemcitabine and cisplatin, and radiotherapy. The median overall survival was 42 months, and the median progression-free survival 25 months, the latter being significantly longer in patients with T1–2 than in those with T3–4 disease (p=0.035). Conclusion: PUCP, a rare but highly aggressive type of prostate cancer, should be considered in men with abnormalities on MRI and normal serum PSA concentrations. Positive GATA-3, P63, and negative PSA are typical immunohistochemistry features. Radical cystectomy and systematic therapies can be effective

Automatically Identifying Teachers' Autonomy Support using Text Classification on Imbalanced Data

Autonomy support is an interpersonal tone of support and understanding. Teachers' instructional behaviors with autonomy support facilitate students' inner motivational resources and enhance their engagement in learning activities. Identifying these behaviors is vital in terms of teaching effects on students' academic performance and behaviors. However, existing methods heavily rely on psychological questionnaires or observers, which are time consuming and difficult to apply in large scale teaching scenarios. In this work, we combine deep neural networks with psychology to achieve automatically identifying the behaviors. To this end, we create the first Chinese instructional behavior dataset for deep learning, and then construct a BERT-based network for modeling psychological features and identifying behaviors. Since frequencies of different behaviors are highly imbalanced, we further design a novel loss function to adaptively optimize training weights for each behavior. Extensive experiments verify the effectiveness of our method and explain how the behaviors are identified

Remote Sensing and Argo Float Observations Reveal Physical Processes Initiating a Winter-Spring Phytoplankton Bloom South of the Kuroshio Current Near Shikoku

BIO-Argo float (chlorophyll a (Chl-a), temperature, and salinity profiles) and remote sensing data (Chl-a, photosynthetic available radiation (PAR), and wind) located south of the Kuroshio current near Shikoku from September 2018 to May 2019 were used to study phytoplankton bloom and their mechanisms of development in open oceans. Results show that higher (lower) Chl-a concentrations are correlated with a deeper (shallower) mixed layer (RPearson = 0.77, Rcrit = 0.12 (alpha = 0.05, n = 263)) compared to the average of Chl-a and mixed layer depth (0.13 mg/m3 and 105 m). The average net accumulation rates (r) of phytoplankton were close to 0.08 d−1. An increasing r corresponds to a gradually increasing surface Chl-a (S (Chl-a): 0–20 m average Chl-a) and integrated Chl-a inventory (I (Chl-a): integrated Chl-a from surface to euphotic depth). These phenomena indicate that the mechanism of winter-spring phytoplankton blooms is consistent with the dilution-recoupling hypotheses (DRH). During the bloom formation, winter deep mixing and eddy-wind Ekman pumping are enhanced by a strong winter monsoon. The enhancement may disturb predator–prey interactions and dilute zooplankton in deep mixed layers. Moreover, winter deep mixing and eddy-wind Ekman pumping can cause the nutrients to be transported into the euphotic layer, which can promote the growth of phytoplankton and increase grazing. During the bloom extinction, the stratification strengthens and the intensity of light increases; this increases grazing and nutrient consumption, and decreases the phytoplankton bloom significantly (S (Chl-a) and I (Chl-a) increase by 0.3 mg/m3 and 27 mg/m2, respectively). The output from a biogeochemistry model shows that nutrients are consistent with the temporal distribution of S (Chl-a) and I (Chl-a). Our results suggest that physical processes (deep winter mixing and eddy-wind Ekman pumping) under the DHR framework are critical factors for winter-spring blooms in open oceans with an anticyclone eddy

Feature Visualization and Attribution Analysis of Confusion for Massive Open Online Course

Thousands of learners are taking massive Open Online courses (MOOCs) in search of self-improvement opportunities. However, the learning process often involves a struggle with confusion, which can adversely affect the course participation experience, leading to dropout halfway through. At the same time, it is impossible for the instructors to recognize and respond “confusion” posts accurately and timely, due to the large volume of registrants. This study aims to develop a robust and interpretable NLP model to identify "confusion" posts that require instructors' immediate attention and to dig deeper into the origin causes of confusion posts according to the type of confusion. We find that posts identified as “confusion” are manifestations of different learner affects pertaining to their informational needs–primarily related to cognitive and social processes. Furthermore, we evaluated the model with a 13% improvement in F1 value compared to previous studies and successfully applied it across unseen domains

Detection of Salmonella DNA and drug-resistance mutation by PCR-based CRISPR-lbCas12a system

Abstract Salmonella is an important foodborne pathogen, which can cause serious public health problems. Rapid and accurate detection of Salmonella infection and drug resistance mutations in patients will provide timely guidance for clinical treatment and avoid disease progression and other related clinical problems. Here, we established a highly sensitive and quick method for Salmonella and drug resistance mutation detection based on polymerase chain reaction (PCR) and CRISPR-lbCas12a system and evaluated its practicability with clinical samples. Specific CRISPR RNAs (crRNAs) and primers are designed for Salmonella DNA and parC gene S80I mutation diagnosis. CrRNAs with and without phosphorylated modification and different crRNA preparation methods are used to assess the effect on the detection system. After optimization, we detected as low as one copy of Salmonella DNA and drug resistance mutation parC S80I with the Salmonella DNA standard. For 94 clinical samples, this method also showed high sensitivity (100%, 95% CI: 84.98–100%) and specificity (98.48%, 95% CI: 90.73–99.92%) with less time (3 h) than plate culture (16 h) and conventional antimicrobial susceptibility testing (over 16 h). Besides, one parC S80I mutant strain was detected, which is consistent with the result of DNA sequencing. Taken together, we established a highly sensitive and specific method for Salmonella infection and parC S80I drug resistance mutation detection with fewer reagents and ordinary instruments. This assay has wide application prospects for fast detection of pathogen (bacterium and virus) infection, drug resistance determination, and proper treatment guidance

Low molecular weight heparin reduces arterial blood lactic acid content and increases estimated glomerular filtration rate in patients with moderate Covid-19 pneumonia

Abstract. Background:. Coronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. We aimed to investigate whether low molecular weight heparin (LMWH) can promote organ function recovery in moderate Covid-19 pneumonia patients. Methods:. We initiated an LMWH protocol in Covid-19 patients with increased D-dimer, body mass index >30 kg/m2 or a history of diabetes from January 18, 2020 at Shanghai Public Health Clinical Center. In this retrospective study, we assigned moderate Covid-19 pneumonia patients admitted between January 18th and April 18, 2020 receiving the LMWH protocol to the LMWH group. Moderate patients who met the inclusion criteria but did not receive LMWH protocol were included in the control group by 1:2 propensity score matching. General clinical information, indicators for renal function, arterial blood gas analyses, arterial blood lactic acid content (mmol/L), and coagulation indexes at 0 day, 3 days, 7 days, and 11 days after admission were recorded and compared between the two groups. Results:. There were 41 patients in the LMWH group and 82 patients in the control group. General information in both groups were similar. Compared to the control group, the arterial blood lactic acid content (mmol/L) at day 11 (1.3 [1.1, 1.7] vs. 1.2 [0.9, 1.3], P = 0.016) was reduced in the LMWH group. The estimated glomerular filtration rate (eGFR) in the LMWH group was higher than that in the control group at day 7 (108.54 [89.11, 128.17] vs. 116.85 [103.39, 133.47], P = 0.039) and day 11 (113.74 [94.49, 126.34] vs. 128.31 [112.75, 144.12], P = 0.003). The serum creatinine levels (Scr) in the LMWH group were lower than that in the control group at day 7 (62.13 [51.47, 77.64] vs. 55.49 [49.50, 65.75], P = 0.038) and day 11 (63.35 [50.17, 75.73] vs. 51.62 [44.62, 61.24], P = 0.005). Conclusions:. LMWH treatment can reduce arterial blood lactic acid levels and improve eGFR in moderate Covid-19 pneumonia patients. Randomized controlled trials are warranted to further investigate this issue. Trial registration:. ChiCTR.org.cn, ChiCTR2000034796

High Serum Level of Soluble Programmed Death Ligand 1 is Associated With a Poor Prognosis in Hodgkin Lymphoma

Blockade of the programmed cell death 1-programmed cell death ligand 1 pathway is a new and promising therapeutic approach in Hodgkin lymphoma (HL). To our knowledge, the impact of soluble programmed cell death ligand 1 (sPD-L1) serum levels on HL patient prognosis has not yet been investigated. In this study, the prognostic value of sPD-L1 was assessed in patients with HL. We measured serum sPD-L1 levels and identified their prognostic value in 108 newly diagnosed HL patients using an enzyme-linked immunosorbent assay (ELISA). We found higher serum sPD-L1 concentrations in HL patients than in healthy controls. The best sPD-L1 cutoff value for predicting disease progression risk was 25.1674 ng/ml. The 4-year progression-free survival (PFS) rates for the high-sPD-L1 and low-sPD-L1 groups were 78.8% and 93.3%, respectively. Multivariate survival analysis showed that advanced stage and higher sPD-L1 levels (>25.1674 ng/ml) were independent prognostic factors for shorter PFS. In addition, higher sPD-L1 levels were positively correlated with advanced stage and negatively correlated with peripheral blood monocyte number. The serum sPD-L1 level is an independent prognostic factor for PFS in HL patients and may allow identification of a subgroup of patients who require more intensive therapy and who may benefit from anti-PD-1 agents