Miracle-dz/UniFAR-FTUs huggingface dataset:
Water quality restoration by harvesting mixed culture microalgae using Moringa oleifera

Excessive growth of microalgae due to use of fertilizers, detergents, and discharge of domestic waste results in the eutrophication and degradation of the water quality of lakes and ponds. The present study aimed to improve the quality of pond water by harvesting mixed cultures of microalgae grown in a pond using Moringa oleifera (MO) extract as a coagulant. The study comprises evaluating the effects of coagulant dose, pH, mixing time, mixing rate, settling time, temperature, and algal biomass concentration on nutrient and microalgae cell removal. The pond water quality restoration was assessed by characterization of raw and MO‐treated water. The MO was found to be very effective for mixed culture microalgae harvesting with flocculation efficiency of 92.97% at dose of 15 ml/L of MO extract, pH 8, mixing time 5 min, mixing rate 30 rpm, and 20‐min settling time. The results have shown significant improvement in pond water quality with reduction in turbidity from 388.16 ± 48.23 to 8.39 ± 1.0 NTU, chlorophyll‐a from 635.01 ± 86.20 to 15.03 ± 1.5 mg/m3, total nitrogen (TN) from 20.37 ± 4.64 to 12.10 ± 1.19 mg/L, and total phosphorus (TP) from 2.05 ± 0.10 to 1.61 ± 0.24 mg/L.
The Acute Effect of Exercise on Executive Function and Attention: Resistance Versus Aerobic Exercise

Acute aerobic exercise was shown to enhance such cognitive functions as executive function (EF) and attention. Acute resistance exercise was also shown to enhance cognitive functions, however, only few studies directly compared these two exercise modalities. The aim of this study was to evaluate the acute effect of a typical moderate intensity resistance exercise session as compared to a typical moderate intensity aerobic session, on executive function and attention. A counterbalanced repeated measures experimental design was applied. Forty physical education students (21 women; 19 men, age = 25.7±2.84 years) were tested before and after three sessions: aerobic, resistance, and control. Each session consisted of 30 minutes of exercise or a rest. Executive function and attention were assessed by components of the computerized Stroop Catch game and Go-NoGo cognitive tests. A two-way ANOVA showed a greater increase in attention scores after the resistance sessions (p < .05) compared to the control condition. Attention scores in the aerobic sessions showed a trend toward improvement but did not reach statistical significance. Scores of EF significantly increased, both after the resistance session and the aerobic session (p < .05), but not after rest in the control condition. Our findings show that an acute session of resistance exercise increased both Attention and EF test scores, while an aerobic exercise session improved only the EF scores.
Convergent Met and voltage-gated Ca2+ channel signaling drives hypermigration of Toxoplasma-infected dendritic cells

ABSTRACT Ras–Erk MAPK signaling controls many of the principal pathways involved in metazoan cell motility, drives metastasis of multiple cancer types and is targeted in chemotherapy. However, its putative roles in immune cell functions or in infections have remained elusive. Here, using primary dendritic cells (DCs) in an infection model with the protozoan Toxoplasma gondii, we show that two pathways activated by infection converge on Ras–Erk MAPK signaling to promote migration of parasitized DCs. We report that signaling through the receptor tyrosine kinase Met (also known as HGF receptor) contributes to T. gondii-induced DC hypermotility. Furthermore, voltage-gated Ca2+ channel (VGCC, subtype CaV1.3) signaling impacted the migratory activation of DCs via calmodulin–calmodulin kinase II. We show that convergent VGCC signaling and Met signaling activate the GTPase Ras to drive Erk1 and Erk2 (also known as MAPK3 and MAPK1, respectively) phosphorylation and hypermotility of T. gondii-infected DCs. The data provide a molecular basis for the hypermigratory mesenchymal-to-amoeboid transition (MAT) of parasitized DCs. This emerging concept suggests that parasitized DCs acquire metastasis-like migratory properties that promote infection-related dissemination. Summary: The parasite T. gondii hijacks the Ras–Erk, Met and Ca2+ signaling machinery to control the migration of immune cells and promote its own dissemination.
Co-infection with SARS-CoV-2 and Influenza A Virus in Patient with Pneumonia, China

We report co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus in a patient with pneumonia in China. The case highlights possible co-detection of known respiratory viruses. We noted low sensitivity of upper respiratory specimens for SARS-CoV-2, which could further complicate recognition of the full extent of disease.
To Compare the Results of Ultrasound Guided Aspiration and Incision and Drainage in the Management of Breast Abscess

: Breast abscess is less common in developed countries due to improved puerperal hygiene, nutrition, early administration of antibiotics and standard of living, breast abscess remains a morbid condition among lactating women in developing countries. Breast abscess is a most common cause of morbidity in puerperal women. Breast abscess ranges from mastitis to deep abscess. The Incidence of lactation breast abscess is high in India. The aim of this study is to compare the results of ultrasound guided aspiration and incision and drainage in the management of breast abscess. This is a comparative study between ultrasound guided aspiration and incision and drainage consist of 50 patients who underwent both the treatment alternatively. Even though recurrence rate is slightly high in USG guided aspiration when compared to incision and drainage, USG guided aspiration is effective method of treatment in breast abscess with good patient satisfaction. Even though recurrence rate is slightly high in USG guided aspiration when compared to incision and drainage, USG guided aspiration is effective method of treatment in breast abscess with good patient satisfaction.
Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects

Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1‐7 and idarubicin (12 mg/m2) on days 1‐3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high‐risk and seven (44%) had standard‐risk cytogenetics. Ten episodes of CRS were observed. No cases of GVHD or treatment‐related mortality were reported. Event‐free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high‐risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor‐specific T cell clones.
Cortical Thickness in Dutch Police Officers: An Examination of Factors Associated with Resilience

Abstract Previous neuroimaging studies on resilience have generally compared resilience and psychopathology after stress exposure, which does not allow for conclusions regarding correlates specific to resilience. The aim of the present study was to investigate resilience‐specific correlates in cortical thickness and/or cortical surface area and their correlations with psychometric measurements, using a three‐group design that included a non–trauma‐exposed control group in order to disentangle effects related to resilience from those related to psychopathology. Structural magnetic resonance imaging scans were acquired from 82 Dutch police officers. Participants were categorized into resilient (n = 31; trauma exposure, no psychopathology), vulnerable (n = 32; trauma exposure, psychopathology), and control groups (n = 19; no trauma exposure, no psychopathology). Specific regions of interest (ROIs) were identified based on previous studies that found the rostral and caudal anterior cingulate cortex (ACC) to be implicated in trauma‐related psychopathology. Cortical thickness and surface area of the ROIs—the rostral and caudal ACC—and of the whole brain were examined. No significant differences in cortical thickness or surface area were found between the resilient group and other groups in the ROI and whole‐brain analyses. Thus, the results of the present study provide no evidence of an association between resilience to traumatic stress and measures of thickness and surface area in cortical regions of the brain in a sample of Dutch police officers.
RSK3 mediates necroptosis by regulating phosphorylation of RIP3 in rat retinal ganglion cells

Receptor‐interacting protein 3 (RIP3) plays an important role in the necroptosis signaling pathway. Our previous studies have shown that the RIP3/mixed lineage kinase domain‐like protein (MLKL)‐mediated necroptosis occurs in retinal ganglion cell line 5 (RGC‐5) following oxygen‐glucose deprivation (OGD). However, upstream regulatory pathways of RIP3 are yet to be uncovered. The purpose of the present study was to investigate the role of p90 ribosomal protein S6 kinase 3 (RSK3) in the phosphorylation of RIP3 in RGC‐5 cell necroptosis following OGD. Our results showed that expression of RSK3, RIP3, and MLKL was upregulated in necroptosis of RGC‐5 after OGD. A computer simulation based on our preliminary results indicated that RSK3 might interact with RIP3, which was subsequently confirmed by co‐immunoprecipitation. Further, we found that the application of a specific RSK inhibitor, LJH685, or rsk3 small interfering RNA (siRNA), downregulated the phosphorylation of RIP3. However, the overexpression of rip3 did not affect the expression of RSK3, thereby indicating that RSK3 could be a possible upstream regulator of RIP3 phosphorylation in OGD‐induced necroptosis of RGC‐5 cells. Moreover, our in vivo results showed that pretreatment with LJH685 before acute high intraocular pressure episodes could reduce the necroptosis of retinal neurons and improve recovery of impaired visual function. Taken together, our findings suggested that RSK3 might work as an upstream regulator of RIP3 phosphorylation during RGC‐5 necroptosis.
Integrative Analysis of Multi-omics Data Identified EGFR and PTGS2 as Key Nodes in a Gene Regulatory Network Related to Immune Phenotypes in Head and Neck Cancer

Purpose: Malignant progression exhibits a tightly orchestrated balance between immune effector response and tolerance. However, underlying molecular principles that drive the establishment and maintenance of the tumor immune phenotype remain to be elucidated. Experimental Design: We trained a novel molecular classifier based on immune cell subsets related to programmed death-ligand 1 (PD-L1) and interferon γ (IFNγ) expression, which revealed distinct subgroups with higher (cluster A) or lower (subcluster B3) cytotoxic immune phenotypes. Integrative analysis of multi-omics data was conducted to identify differences in genetic and epigenetic landscapes as well as their impact on differentially expressed genes (DEG) among immune phenotypes. A prognostic gene signature for immune checkpoint inhibition (ICI) was established by a least absolute shrinkage and selection operator (LASSO)-Cox regression model. Results: Mutational landscape analyses unraveled a higher frequency of CASP8 somatic mutations in subcluster A1, while subcluster B3 exhibited a characteristic pattern of copy-number alterations affecting chemokine signaling and immune effector response. The integrative multi-omics approach identified EGFR and PTGS2 as key nodes in a gene regulatory network related to the immune phenotype, and several DEGs related to the immune phenotypes were affected by EGFR inhibition in tumor cell lines. Finally, we established a prognostic gene signature by a LASSO-Cox regression model based on DEGs between nonprogressive disease and progressive disease subgroups for ICI. Conclusions: Our data highlight a complex interplay between genetic and epigenetic events in the establishment of the tumor immune phenotype and provide compelling experimental evidence that a patient with squamous cell carcinoma of the head and neck at higher risk for ICI treatment failure might benefit from a combination with EGFR inhibition.
Randomized, Double-Blind, Placebo-Controlled, Dose and Schedule-Finding Study of AMG 531 In Chemotherapy-Induced Thrombocytopenia (CIT): Results of a Phase I/II Study.

Abstract 1544 AMG 531 is a peptibody that increases platelet production by stimulating thrombopoietin (TPO) receptors. Prior studies (Vadhan-Raj et al, JCO 2003) have shown the importance of schedule of recombinant TPO to overcome thrombocytopenia (TCP) caused by high dose chemotherapy (CT). RHyper-CVAD alternating with RArac-MTX is a highly effective regimen in the treatment of aggressive non-Hodgkin9s lymphoma (NHL), including Mantle-cell lymphoma, with severe TCP as dose-limiting toxicity (86% grade 4 TCP in cycle-2). The objectives of this study were to evaluate the clinical safety and preliminary efficacy of AMG 531 in CIT. Cohorts of 12 evaluable patients were enrolled sequentially at each of the 3 dose levels (1, 3, or 10 mcg/kg). Patients at each dose level were randomized 1:1 into Arm A (pre/post dosing) or Arm B (post-dosing only). All pts received CT alone in cycle-1. In cycle-2, all pts received blinded study drug (2:1 AMG 531 or placebo). The study drug was administered SC as 2 doses given on days -5 and 5 (pre and post doses-Arm A), or on days 5 and 7 (only post-chemotherapy doses-Arm B). In subsequent cycles of CT (maximum total 6 cycles), all pts, including placebo group, received open-label AMG 531 by the same schedule. Of the 50 pts enrolled, 41 received at least one dose of AMG 531 and are evaluable for toxicity and 36 received the treatment with the study drug as per protocol and are evaluable for response. Treatment with AMG 531 was generally well tolerated, with some pts experiencing mild to moderate headache, myalgia, bone pain, and thrombocytosis and venous thromboembolism [4 pts; 2 deep vein thrombosis (DVT) and 2 pulmonary embolism (PE); both at 10 mcg/kg]. Four of the 9 pts who did not receive the study drug also experienced DVT (3 pts) or PE (1 pt). The platelet nadir was significantly higher and the duration of TCP was shorter, with a reduced need for the PLT transfusions on Arm A (pre and post-dosing) compared to placebo as shown in the table below. There was reduced TCP on Arm B (post-dosing) as compared to placebo, but not statistically significant. There were also fewer patients with bleeding episodes (all grades) on Arm A vs placebo (1/12 pts vs 6/12 pts, p = 0.07, Fisher9s exact test) in the blinded-cycle. Using general-linear model, there was a difference in schedule (p=0.0466) and difference in doses (p=0.0162) on duration of TCP, and the lower doses (1 or 3 mcg/kg) appeared to have a better biologic activity than higher dose (10mcg/kg) as compared to the placebo. Conclusions: AMG 531 was generally well tolerated and significantly reduced severe thrombocytopenia when administered both before and after (pre and post dosing) CT in NHL pts. Future larger studies are needed to establish the safety and efficacy of AMG 531 in CIT. Disclosures: Vadhan-Raj:Amgen: Honoraria, Research Funding. Off Label Use: AMG 531 (Romiplostim) for chemotherapy-induced thrombocytopenia.
Long‐term efficacy and predictive correlates of response to nivolumab in Japanese patients with esophageal cancer

The long‐term efficacy of nivolumab in esophageal squamous cell carcinoma and its association with disease biomarkers are currently not well known. Therefore, we investigated the association in Japanese patients with treatment‐refractory advanced esophageal cancer who participated in an open‐label, single‐arm, multicenter phase II study. Patients received nivolumab 3 mg/kg i.v. every 2 weeks until disease progression or unacceptable toxicity, and were followed up for 2 years after the initial dosing of the last patient. Archival tissue samples were collected before treatment and analyzed for programmed death ligand‐1 (PD‐L1) and CD8+ status of tumors and tumor‐infiltrating lymphocytes (TILs) and human leukocyte antigen class 1. Efficacy end‐points included objective response rate (ORR), overall survival (OS), progression‐free survival (PFS), time to response, and duration of response. Of 65 enrolled patients (83% male), 64 were evaluable for efficacy and 41 (63%) for biomarkers. The ORR, median OS, and survival rate were 17.2%, 10.78 months, and 17.2%, respectively. Time to response was 1.45 months and duration of response was 11.17 months. The PD‐L1 positivity of tumor cells was possibly associated with better PFS (2.04 vs 1.41 months, cut‐off 1%) and OS (11.33 vs 6.24 months, cut‐off 1%). Median OS was prolonged in patients with a median number of TILs greater than 63.75% vs 63.75% or less (11.33 vs 7.85 months). Nivolumab showed continued long‐term efficacy, as seen by the stability of PFS and OS, in Japanese patients with esophageal squamous cell carcinoma. Further investigation of PD‐L1 tumor expression and TILs as potential biomarkers for predicting patients likely to benefit from nivolumab therapy is warranted.
Impact of Single Combination Inhaler versus Multiple Inhalers to Deliver the Same Medications for Patients with Asthma or COPD: A Systematic Literature Review

Abstract With increasing choice of medications and devices for asthma and chronic obstructive pulmonary disease (COPD) treatment, comparative evidence may inform treatment decisions. This systematic literature review assessed clinical and economic evidence for using a single combination inhaler versus multiple inhalers to deliver the same medication for patients with asthma or COPD. In 2016, Embase, PubMed and the Cochrane library were searched for publications reporting studies in asthma or COPD comparing a single-inhaler combination medicine with multiple inhalers delivering the same medication. Publications included English-language articles published since 1996 and congress abstracts since 2013. Clinical, economic and adherence endpoints were assessed. Of 2031 abstracts screened, 18 randomized controlled trials (RCTs) in asthma and four in COPD, nine retrospective and three prospective observational studies in asthma, and four observational studies in COPD were identified. Of these, five retrospective and one prospective study in asthma, and two retrospective studies in COPD reported greater adherence with a single inhaler than multiple inhalers. Nine observational studies reported significantly (n=7) or numerically (n=2) higher rates of adherence with single- versus multiple-inhaler therapy. Economic analyses from retrospective and prospective studies showed that use of single-inhaler therapies was associated with reduced healthcare resource use (n=6) and was cost-effective (n=5) compared with multiple-inhaler therapies. Findings in 18 asthma RCTs and one prospective study reporting lung function, and six RCTs reporting exacerbation rates, showed no significant differences between a single inhaler and multiple inhalers. This was in contrast to several observational studies reporting reductions in healthcare resource use or exacerbation events with single-inhaler treatment, compared with multiple inhalers. Retrospective and prospective studies showed that single-inhaler use was associated with decreased healthcare resource utilization and improved cost-effectiveness compared with multiple inhalers. Lung function and exacerbation rates were mostly comparable in the RCTs, possibly due to study design.
The Arabidopsis SAFEGUARD1 suppresses singlet oxygen-induced stress responses by protecting grana margins

Significance Singlet oxygen (1O2) generated in the Arabidopsis fluorescent (flu) mutant triggers cell death in young seedlings and inhibits growth of mature plants through the EXECUTER1 (EX1)-dependent retrograde signaling pathway. Here, we show another 1O2-induced chloroplast-to-nucleus retrograde signaling pathway, the 1O2-SAFEGUARD1 (SAFE1) pathway that is independent of EX1. SAFE1 is localized in the chloroplast stroma, and release of 1O2 induces SAFE1 degradation via chloroplast-originated vesicles. Without SAFE1, grana margins (GMs) of chloroplast thylakoids are specifically damaged upon 1O2 generation and associate with plastoglobules. We suggest that the Arabidopsis SAFE1 suppresses 1O2-induced stress responses by protecting GMs. Our paper, therefore, uncovers an additional 1O2-induced pathway and a unique mechanism by which higher plants deal with oxidative stress. Singlet oxygen (1O2), the major reactive oxygen species (ROS) produced in chloroplasts, has been demonstrated recently to be a highly versatile signal that induces various stress responses. In the fluorescent (flu) mutant, its release causes seedling lethality and inhibits mature plant growth. However, these drastic phenotypes are suppressed when EXECUTER1 (EX1) is absent in the flu ex1 double mutant. We identified SAFEGUARD1 (SAFE1) in a screen of ethyl methanesulfonate (EMS) mutagenized flu ex1 plants for suppressor mutants with a flu-like phenotype. In flu ex1 safe1, all 1O2-induced responses, including transcriptional rewiring of nuclear gene expression, return to levels, such as, or even higher than, those in flu. Without SAFE1, grana margins (GMs) of chloroplast thylakoids (Thys) are specifically damaged upon 1O2 generation and associate with plastoglobules (PGs). SAFE1 is localized in the chloroplast stroma, and release of 1O2 induces SAFE1 degradation via chloroplast-originated vesicles. Our paper demonstrates that flu-produced 1O2 triggers an EX1-independent signaling pathway and proves that SAFE1 suppresses this signaling pathway by protecting GMs.
The impact of intravenous opioid shortages on postoperative pain control in a pediatric cardiac intensive care unit

The national supply of intravenous pain medications has been restricted since 2018 due to shortages. In late 2017, the ongoing shortages combined with the increased demand for alternative formulations resulted in interruptions in the supply of medications. The cascading effect of interruptions in supply caused hospitals to implement restrictive measures to extend the availability of these medications. This study aims to evaluate differences in pain control in postoperative cardiac patients due to intravenous opioid shortage at a standalone pediatric hospital.