Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of n-3 polyunsaturated fatty acids on dopaminergic neurons in substantia nigra, brain inflammatory response and behavior in mice with Parkinson’s disease

Purpose: To examine the effect of n-3 polyunsaturated fatty acids (PUFAs) on dopaminergic neurons in substantia nigra, intracerebral inflammatory response and ethology in mice with Parkinson’s disease (PD). Methods: Four groups of male C57BL/6 mice (n = 48) were used: normal control, negative control, n3PUFA, and Madopa groups. Except for normal control group, all groups were given 6- hydroxydopamine hydrochloride (6-OHDA) to establish Parkinson’s mice model. The expressions of tyrosine hydroxylase (TH) and calcium-binding protein (CB) in substantia nigra dopaminergic neurons were determined with immunohistochemistry and Western blot. The contents of nitric oxide (NO), tumor necrosis factor (TNF-α) and interferon γ (IFN-γ) (indices of intracerebral inflammatory response) were measured. Tremor paralysis, moving grid number, standing times, swimming ability, and the number of rollers in each group were observed as indices of ethology. Results: The number of TH and CB-positive neurons in the substantia nigra of n-3PUFA-treated mice was significantly increased, relative to those in Madopa-treated mice (p < 0.05). The expressions of TH and CB proteins in substantia nigra in n-3PUFA group were markedly higher than the corresponding expressions in Madopa-treated mice (p < 0.05). Decreased levels of NO, TNF-α and IFN-γ levels were seen in 3PUFA group, when compared to mice in Madopa group, but higher behavioral scores were obtained in n-3PUFA-treated mice, relative to Madopa-treated mice (p < 0.05). Conclusion: The n-3PUFAs protect substantia nigra compact dopaminergic neurons against Parkinson’s disease, alleviate immune inflammation, and improve the coordination of limb movement. Thus, n-3PUFAs have potential therapeutic application in the management of Parkinson’s disease.
The source of uncertainty in projecting the anomalous western North Pacific anticyclone during El Niño–decaying summers

The western North Pacific anomalous anticyclone (WNPAC) is a key bridge that links El Niño and East Asian climate variability. Future projections of ENSO-related WNPAC changes under global warming are highly uncertain across climate models. Based on a 40-member ensemble from the Community Earth System Model Large Ensemble (CESM-LE) project, we investigate the effects of internal variability on the El Niño-related WNPAC projection. Here, we first develop a decomposition method to separate the contributions of El Niño amplitude change and non-amplitude change from the leading uncertainty in the El Niño-related WNPAC projection. Based on the decomposition, approximately 23% of the uncertainty in the El Niño-related WNPAC projection is attributed to the El Niño amplitude change, while the remaining 77% is from the non-amplitude change, which is mainly related to the change in the El Niño decaying pace. A larger (smaller) El Niño amplitude can enhance (weaken) the WNPAC through a stronger (weaker) tropical Indian Ocean (TIO) capacitor effect. For non-amplitude change, a faster (slower) El Niño decaying pace can also enhance (weaken) the WNPAC through descending Rossby waves in response to cold sea surface temperature anomalies (SSTA) over the tropical central-eastern Pacific. The decomposition method can be generalized to investigate the sources of uncertainty related to El Niño properties in climate projections and to help improve the understanding of changes in the interannual variability of East Asian-western Pacific climate under global warming.
HYDROTROPY: A PROMISING TOOL FOR SOLUBILITY ENHANCEMENT: A REVIEW

The study on solubility yields information about the structure and intermolecular forces of drugs. Use of the solubility characteristics in bioavailability, pharmacological action and solubility enhancement of various poorly soluble compounds is a challenging task for researchers and pharmaceutical scientists. Hydrotropy is one of the solubility enhancement techniques which enhance solubility to many folds with use of hydrotropes like sodium benzoate, sodium citrate, urea, niacinamide etc. and have many advantages like; it does not require chemical modification of hydrophobic drugs, use of organic solvents, or preparation of emulsion system etc.
A phase I dose-escalation study of the MDM2-p53 antagonist BI 907828 in patients (pts) with advanced solid tumors.

3016 Background: BI 907828, a highly potent and orally administered MDM2-p53 antagonist, showed antitumor efficacy in vivo, especially in TP53 wild-type MDM2-amplified de-differentiated liposarcoma (DDLPS) patient-derived xenografts and syngeneic models. Methods: NCT03449381 is a phase I study of BI 907828 in pts with solid tumors. The objectives of the dose-escalation part were to determine the maximum tolerated dose (MTD) based on the frequency of pts with dose-limiting toxicities (DLTs) during cycle 1, determine the recommended dose for expansion, and evaluate the safety and tolerability of two dosing schedules: BI 907828 given on day 1 of 21-day cycles (Arm A) or days 1 and 8 of 28-day cycles (Arm B). Dose escalation was guided by a Bayesian logistic regression model. The secondary objectives include pharmacokinetics (PK), pharmacodynamics and antitumor activity. Results: At January 15, 2021, 54 pts with advanced solid tumors (median of 2 lines of prior systemic therapies; range 0–11) were treated with BI 907828 (Arm A, 29 pts, dose range 10–80 mg; Arm B, 25 pts, dose range 5–60 mg). In Arm A, 5 pts experienced DLTs in cycle 1, including one Grade (Gr) 3 Nausea and one Gr 3 Thrombocytopenia at 45 mg, one Gr 3 Enterocolitis at 60 mg, and one Gr 4 Neutropenia and one Gr 4 Thrombocytopenia at 80 mg. In Arm B, 3 DLTs were reported: one Gr 4 Thrombocytopenia at 45 mg, one Gr 4 Neutropenia associated with Gr 4 Thrombocytopenia, and one Gr 3 Neutropenia at 60 mg. The most common Gr 3/4 treatment-related adverse events (AEs) were Thrombocytopenia (28.6%), Neutropenia (10.7%) and Nausea (10.7%) in Arm A, and Thrombocytopenia (16.6%) and Neutropenia (12.5%) in Arm B. Preliminary PK data indicate that BI 907828 reaches Tmax at 4–6 h. Mean plasma exposures (Cmax and AUC0-inf) increased with dose. The geometric mean (gMean) Clearance/F was 5–19 mL/min and the gMean apparent volume of distribution was 23–57 L. The gMean half-lives estimated after the 1st dose were 26–55 h. Inter-patient variability in exposure was moderate. An increase in the target engagement biomarker GDF-15 in plasma was observed. The mean fold-change from baseline ranged from 8 to 49. Antitumor activity was seen in both schedules. In Arm A, a confirmed PR was seen in 2 pts with MDM2-amplified LPS (one PR lasted > 2 years) and SD in 17 pts. In Arm B, 2 pts had PR (one confirmed in MDM2-amplified LPS and one not yet confirmed in MDM2-amplified pancreatic adenocarcinoma) and 14 had SD. Of note, 5 of 10 pts with DDLPS were progression-free for ≥9 months. Conclusions: BI 907828 showed a manageable safety profile, favorable PK properties and early signs of efficacy, especially in MDM2-amplified tumors. With both dosing regimens, DLTs were Neutropenia and Thrombocytopenia. Non-hematologic AEs, mainly gastrointestinal, were mostly low-grade and not dose-limiting. The MTD of 60 mg in Arm A (day 1 of 21-day cycles) and 45 mg in Arm B (days 1 and 8 of 28-day cycles) are awaiting confirmation. Clinical trial information: NCT03449381.
Perception of Students and Faculty Members of the Impact of a Preparatory Year Program on the Students of Health Professions Education Colleges

Objective: The Preparatory Year Program (PYP) is a one-year preparatory program to prepare students for a full multi-year degree curriculum. It offers a bridge between students’ high-school and university-level studies. The study aimed at evaluating the impact of the King Abdulaziz University preparatory year program on students of the health professions education colleges from both students' and faculty viewpoints. Methods: This is a descriptive study that depended on the collection of data from both students and faculty members based on their perceptions. It was conducted during the period from May 2019 to January 2020. Data was collected from students through self-administered questionnaires and from faculty members through structured interviews. Descriptive statistics were applied. Results: Around half of the students agreed that the preparatory year made them self-confident and reinforced their discipline (49.2% and 46.9%, respectively). Less than two-thirds agreed that the preparatory year reinforced their sense of responsibility and helped them adapt to the university educational environment (60.6% and 64.3%, respectively). On the other hand, more than half of them (58.5%) disagreed that the preparatory year classes helped them select their majors. Also, more than half of them (57.2%) disagreed that the preparatory year prepared them for their major classes. Conclusion: The impact of the preparatory year on students of the health professions colleges is weak. This is the opinion of both students and faculty members. In-depth studies are needed to further investigate this impact. Keywords: Universities; Health Occupations; Undergraduate; Curriculum; Saudi Arabia.
OPTIC primary analysis: A dose-optimization study of 3 starting doses of ponatinib (PON).

7000 Background: PON, a third-generation tyrosine kinase inhibitor (TKI), demonstrated deep and long-lasting responses and survival in patients (pts) with chronic-phase chronic myeloid leukemia (CP-CML) resistant/intolerant to second-generation TKI therapy (PACE; NCT01207440); post hoc analysis suggested a relationship between dose and both adverse events and response. Here we present the primary analysis of OPTIC (NCT02467270), an ongoing, randomized, phase 2 trial with a novel response-based dosing regimen of PON in pts with resistant/intolerant CP-CML. Methods: Pts with CP-CML resistant/intolerant to ≥2 TKIs or with the BCR-ABL1 T315I mutation were randomized to PON starting doses of 45 mg (cohort A; 45 mg → 15 mg), 30 mg (B; 30 mg →15 mg), and 15 mg (C) once daily. Doses were reduced to 15 mg with achievement of ≤1% BCR-ABL1IS in cohorts A and B. The primary endpoint is ≤1% BCR-ABL1IS at 12 mo; secondary endpoints include cytogenetic and molecular responses and safety outcomes. AOEs were adjudicated prospectively by an independent review committee. Results: 283 pts were randomized (A/B/C: n=94/95/94) and had the following baseline characteristics: median age 48 y (18‒81 y); 98% received ≥2 (55% ≥3) TKIs; 99% had resistant disease; 40% had ≥1 baseline mutations (23% T315I). At the primary analysis with 32 mo median follow-up, 134 pts (47%; n=50/41/43) remained on treatment and 204 pts (72%) had PON exposure ≥12 mo. At 12 mo, 44% (41/93) in A, 29% (27/93) in B, and 23% (21/91) in C achieved ≤1% BCR-ABL1IS (Table); primary endpoint was met by cohort A. Dose reductions to 15 mg after achieving response (A/B) were 48/29%. Most common grades ≥3 TEAEs were thrombocytopenia, 27%; neutropenia, 17%; and anemia, 7%. AOEs/serious AOEs were reported in cohorts A (10%/4%), B (5%/4%), and C (3%/3%). Dose reductions or discontinuations for TEAEs (A/B/C) were 46/35/32% and 19/16/14%, respectively. Conclusions: The OPTIC primary analysis demonstrates the optimal benefit:risk profile for PON was achieved with a response-based dosing regimen starting with 45 mg/d, followed by dose reduction to 15 mg/d upon achieving ≤ 1% BCR-ABL1IS; 30 mg→15 mg and 15 mg cohorts may provide benefit, especially in pts without T315I mutation (Table). The observed ≤1% BCR-ABL1IS responses are supported by robust survival outcomes in pts with CP-CML resistant to second-generation BCR-ABL1 TKI therapy, both with and without BCR-ABL1 mutations. Clinical trial information: NCT02467270. [Table: see text]
20 Years of IEEE Sensors Journal

The IEEE Sensors Journal was born on June 1, 2001, when its first ever issue was published. The journal has grown exponentially over the past 20 years to become one of the world’s largest journals in sensor engineering and technology as well as one of the largest among more than 200 IEEE publications. In these 20 years, the field of sensors has dramatically changed of course: Completely new areas have emerged, e.g., body sensor networks, the Internet-of-Things, memristive sensors, or the smart sensory dusts, while some others have enormously grown, e.g., mechanical sensors, fiber-optics sensors, or radiation sensors. In all these cases, the IEEE Sensors Journal has recorded and presented the progress and achievements of the field. As any engineering journal, IEEE Sensors Journal has also served the community by reporting extremely useful technical papers, in order to provide experiential knowledge. As well, the journal has published scientific manuscripts proposing new detection principles and novel sensing devices. After 20 years of activity, it is now the right time to look back critically at what the field has produced in terms of great achievements and, at the same time, to look ahead at the challenges for the next 20 years to come. That is the main aim of this Special Issue published to celebrate the 20th anniversary of the IEEE Sensors Journal. With this introductory article, we would like to give an overview of the past 20 years by commenting on their highly successful developments.
Effect of cadmium and lead on growth, biochemical parameters and uptake in Lemna polyrrhiza L.

Aquatic plants are known to accumulate heavy metals. In this study, Duckweed plants (Lemna polyrrhiza L.) were exposed to different concentrations of Cd and Pb. Various physio-biochemical parameters (fresh weight, chlorophyll content, soluble protein, soluble sugars, proline content and metal absorption) were studied. At lower metal concentrations, an increase in proline, protein and sugar was observed but at higher concentrations (above 30 mg/l) their decrease was noticed. Uptake of the metals was concentration and time dependent. Treatment with 1, 10 and 20 mg/l of Cd and Pb showed synergistic relation while 30 and 40 mg/l treatments showed antagonistic relation during the metal uptake. The results suggest that the L. polyrrhiza can be effectively used as a phytoremediator for wastewater polluted with more than one heavy metal at moderate concentrations.
Compassion Satisfaction, Compassion Fatigue and Mental-Well Being among Health Care Workers during COVID-19 outbreak

Health care workers have been showing up to provide medical care and assistance to patients even during a global pandemic of Covid-19. Their work has affected their lives, both positively and negatively. Both Compassion Satisfaction and Compassion Fatigue can be an outcome of their hard work and empathy. In light of this unprecedented crisis, it has become crucial to acknowledge the medical fraternity’s mental health status. The present research aims to study compassion satisfaction, burnout, secondary traumatic stress, and mental well-being among health care workers. 84 professionals (physicians, nurses, pharmacists, and technicians) participated in this study. Standardized scales were used to assess compassion satisfaction, compassion fatigue, and mental well-being. The results revealed that there is a negative correlation between burnout and mental well-being among healthcare workers. Secondary traumatic stress and burnout also came out to be positively correlated. Another finding showed that women have higher stress levels as compared to men. Thus, it is necessary to implement mental health interventions among professionals to promote psychological care and reduce stress levels. It is also essential to incorporate the responsibility of institutions in this regard. Regardless of the pandemic, long-term interventions are needed to improve compassion skills among health care workers.
Diversity of Leaf Stomatal Traits among Coffea canephora Pierre ex A. Froehner Genotypes

Leaf morpho-anatomical characteristics directly reflect photosynthetic performance and the ability to adapt to different environmental conditions. The study of biometric traits is essential for the selection of promising plant materials for breeding purposes. To identify new varieties of coffee plants with desirable traits for genetic improvement programs, this study investigated the variability of leaf morpho-anatomical traits in 43 genotypes of Coffea canephora (as the species under study is hypostomatous). Seven leaf characteristics were used: epidermal cell density (ECD), stomatal length (SL), stomatal width (SW), stomatal density (SD), stomatal size (SS), stomatal index (SI), and stomatal length/width. Morphological traits (plant height, internodal distance, and leaf area) and grain production were also assessed. The data analyzed multivariate analysis of variance grouped by the unweighted pair group the arithmetic mean hierarchical method, and data were also subjected to a Pearson linear correlation and principal component analyses (PCAs). The results showed wide morphological variability reflecting six morphological groups, which is relevant for the genetic divergence analysis and for breeding purposes, as the results have the potential to identify superior genotypes. Within the groups, genotypes were mainly separated by the number of epidermal cells and the number and size of the stomata, reflecting a high genetic heterogeneity within genotypes. Positive and negative correlations were found, with levels of significance ranging from weak to strong among the analyzed traits. The highest correlation levels were found for SL × SS, SW × SS, and SI × SD. In addition, the PCA indicated that plant height, distance between nodes, and leaf area were positively correlated and associated. The greater the number and width of stomata, the higher the rate of gas exchange. Both characteristics are favorable for the development and production of coffee plants, explaining the positive correlation observed in this study. These results emphasize the usefulness of trait evaluations for the identification and breeding of genotypes to compose new C. canephora cultivars suitable for changing environments.
Staging Encounters with the End in Pre-Apocalyptic-Post-3.11 Japan

ABSTRAC This paper offers a critical engagement with endings in relation to formulations of crisis and futures through two sites that stage an encounter with the end. The first is the permanent exhibit at Japan’s National Museum of Emerging Science and Innovation in Tokyo. This site, I show, asks us to reflect on how we think about the end of civilisation as an immanent crisis to be overcome through an innovation that allows us to escape accountability for conditions in the present. As such, I argue, it ultimately encourages us to cultivate attention and accountability toward material and conceptual problems in the present. The discussion then takes the idea of cultivating attention to the present to northeast Japan. I show there how an ending inflicted on the coastal residents by the tsunami of March 2011 has made space for precisely this kind of attention and accountability to the present.
Evaluation of Insertion/deletion (I/D) Polymorphisms of ACE Gene in Congenital Anomalies of The Kidney and Urinary Tract From a Brazilian Pediatric Population

Background: Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) are defined as a heterogeneous group of anomalies that resulted from defects in kidney and urinary tract embryogenesis. CAKUT have a complex etiology. Genetic, epigenetic and environmental factors have been investigated in this context. Angiotensin II is a potent vasoconstrictor and exerts an important role in kidney embryogenesis. The angiotensin-converting enzyme (ACE) converts Angiotensin I into Angiotensin II and ACE gene has insertion/deletion (I/D) polymorphisms that have been evaluated in several nephropathies. This study aimed to evaluate whether the I/D polymorphisms of ACE gene are associated with any CAKUT phenotype or CAKUT in general. Methods and Results: Our study was performed with 225 pediatric patients diagnosed with CAKUT and 210 age-and-sex matched healthy controls. ACE I/D alleles were analysed by real-time polymerase chain reaction (RT-PCR). The distribution of ACE I/D polymorphisms were compared between CAKUT patients and healthy controls, as well between ureteropelvic junction obstruction (UPJO), vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK) phenotypes and control group. No statistical association of ACE I/D genotypes and allelic frequency between patients and controls was found among general CAKUT and UPJO, VUR and MCDK phenotypes. Conclusion: Although CAKUT is a complex disease and the ACE gene may exert a role in kidney embryogenesis, CAKUT was not associated with any ACE I/D polymorphisms in this Brazilian pediatric population.
Intra- and Inter-Rater Reliability of a Well-Used and a Less-Used IsoMed 2000 Dynamometer for Knee Flexion and Extension Peak Torque Measurements in a Concentric Test in Athletes

This study aimed to evaluate the intra- and inter-rater reliability of a well-used and a less-used IsoMed-2000 dynamometer for knee flexion and extension peak torque (PT) measurements in a concentric test in athletes. Two IsoMed-2000 isokinetic dynamometers were used, an old one that was well-used and a new one that was less-used. Thirty-seven weight-lifting athletes (12 female, 25 male) were included in this study. Both legs of each athlete were tested twice on each isokinetic dynamometer at 60°/s and 180°/s. The Intraclass Correlation Coefficients (ICC), Standard Error Measurement (SEM), Smallest Detectable Change (SDC), SDC% and 95% limits of agreement were calculated to evaluate the intra- and inter-rater reliability of a well-used and a less-used IsoMed 2000 dynamometer for knee flexion and extension peak torque in athletes. Intra-rater reliability was moderate to excellent (ICCs: 0.516–0.928) for knee muscle strength parameters, and the highest SDC and SEM values were 0.76 N/kg and 0.28 N/kg, respectively. Inter-rater reliability was moderate to excellent (ICCs: 0.519–915) for knee muscle strength parameters, and the highest SDC and SEM values were 0.81 N/kg and 0.29 N/kg, respectively. At least 89.2% of the obtained values of parameters fell within the 95% limits of agreement. Our findings demonstrate the intra and inter-rater reliability of a Well-Used and a Less-Used IsoMed 2000 Dynamometer for Knee Flexion and Extension Peak Torque in Athletes.
Membranotropic Peptide-Functionalized Poly(lactide)-graft-poly(ethylene glycol) Brush Copolymers for Intracellular Delivery

A biodegradable delivery scaffold based on poly(lactide)-graft-poly(ethylene glycol) (PLA-g-PEG) is introduced and tested in vitro. The use of a functional ring-opening polymerization initiator (containing a masked aldehyde) on an azido PEG-lactide monomer combines two known methodologies to afford functionalized PLA. The resulting copolymer features two compatible functional groups and decreased hydrophobicity due to the PEG. The functional groups are capable of performing high-yielding orthogonal postpolymerization reactions, namely strain-promoted azide–alkyne click chemistry and reductive amination. PLA-g-PEG was functionalized with a fluorescent dye (7-nitrobenzoxadiazole, NBD) and a cell internalization peptide, gH625. The resulting delivery vehicle was investigated for cell uptake with HeLa cells, showing that the gH625 conjugation exhibited enhanced cellular uptake and localization in close proximity to the nuclei. The presented methodology is a new approach toward targeted delivery.