Miracle-dz/UniFAR-FTUs huggingface dataset:
Perspectives of Egyptian Research Ethics Committees regarding Their Effective Functioning

The recent increase in research in the Middle East has been associated with the establishment of research ethics committees (RECs). Our aim was to obtain perspectives of RECs regarding the challenges that impede their effective functioning. We conducted in-depth interviews using a semi-structured interview guide. We transcribed and analyzed the interviews to uncover major themes and subthemes. We identified the following themes: Membership composition; Revised training needs of members; Revised availability of human and capital resources; Revised role of the national government; Revised concerns with the informed consent process; Revised government scrutiny of research; Revised investigator-related issues; Revised and concerns with transfer of biological samples to other countries. Our interview study revealed several barriers that need to be considered by appropriate stakeholders to enhance adequate functioning of RECs.
Randomized comparison of imipenem/cilastatin and ceftazidime in the empiric therapy of severe abdominal infections. A multicenter study.

SummaryFifty-six patients with severe intra-abdominal infection have been included in a controlled randomized open study. Imipenem/cilastatin was administered to 28 patients. The remaining 28 patients received ceftazidime, including 7 patients who received a combination of ceftazidime with metronidazole. The difference in cure rates did not reach statistical difference, although 3 failures were reported in the ceftazidime group and none in the imipenem/cilastatin group.Based on 100 pretreatment antibiograms, far more organisms were susceptible to imipencm (99) than to ceftazidime (80) (p < 0.001). The Presence of a pathogen resistant to therapy in the follow-up culture was observed more frequently in the ceftazidime group (p < 0.05). Tolerance and safety profile were good in both groups.It is concluded that imipenem/cilastatin is an efficient empiric monotherapy in severe intra-abdominal infections.
Autistic traits in a population-based ADHD twin sample.

BACKGROUND Most diagnostic nomenclatures do not allow for the concurrent diagnosis of autism and attention-deficit/hyperactivity disorder (ADHD). Clinic-based studies suggest autistic symptoms are common in children with ADHD, but such studies are prone to referral bias. This study assesses whether children with ADHD selected from the general twin population have elevated levels of autistic traits. METHODS Nine hundred forty-six twins identified by Missouri birth records were assigned to DSM-IV ADHD diagnoses and seven population-derived ADHD subtypes defined through latent class analysis of DSM-IV ADHD symptoms. The Social Responsiveness Scale (SRS) was used as a quantitative measure of autistic traits. Linear regression was used to evaluate whether mean SRS scores differed between ADHD diagnostic groups. RESULTS Mean SRS scores for DSM-IV predominantly inattentive subtype and combined subtype ADHD groups were significantly higher than for subjects without DSM-IV ADHD (p < .001, both comparisons). Five of the population-derived ADHD subtypes (talkative-impulsive, mild and severe inattentive, mild and severe combined) had significantly higher mean SRS scores compared to the latent class subtype with few ADHD symptoms (p < .001, all comparisons). DSM-IV combined subtype and the population-derived severe combined subtype had the highest mean total SRS scores and the highest mean scores for each of the three autism symptom domains, with a substantial proportion of individuals scoring in the clinically significant range. CONCLUSIONS This study provides population-based evidence for clinically significant elevations of autistic traits in children meeting diagnostic criteria for ADHD. These results have implications for the design and interpretation of studies of both disorders.
Climatology and Trend of Severe Drought Events in the State of Sao Paulo, Brazil, during the 20th Century

Drought is a natural hazard with critical societal and economic consequences to millions of people around the world. In this paper, we present the climatology of severe drought events that occurred during the 20th century in the region of Sao Paulo, Brazil. To account for the effects of rainfall deficit and changes in temperature at a climatic timescale, we chose the Standardized Precipitation Evapotranspiration Index (SPEI) to identify severe droughts over the city of Sao Paulo, and the eastern and central-western regions of the state. Events were identified using weather station data and European Centre for Medium-Range Weather Forecast (ECMWF) reanalysis data, in order to assess the representation of drought periods in both datasets. Results show that the reanalysis seems suitable to represent the number of events and their mean duration, severity and intensity, but the timing and characteristics of individual events are not well reproduced. The correlation between observation and reanalysis SPEI time series is low to moderate in all cases. A linear trend analysis between 1901 and 2010 shows a tendency of increasing (decreasing) severe drought events in the central and western (eastern) Sao Paulo state, according to observational data. This is in agreement with previous findings, and the reanalysis presents this same signal. The weakened trend values in the reanalysis may be associated with issues in representing precipitation in this dataset.
The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, control HIF1α prolyl hydroxylation by regulating cellular iron levels

Hypoxia Inducible transcription Factors (HIFs) are principally regulated by the 2-oxoglutarate and Iron(II) prolyl hydroxylase (PHD) enzymes, which hydroxylate the HIFα subunit, facilitating its proteasome-mediated degradation. Observations that HIFα hydroxylation can be impaired even when oxygen is sufficient emphasise the importance of understanding the complex nature of PHD regulation. Here, we use an unbiased genome-wide genetic screen in near-haploid human cells to uncover cellular processes that regulate HIF1α. We identify that genetic disruption of the Vacuolar H+ ATPase (V-ATPase), the key proton pump for endo-lysosomal acidification, and two previously uncharacterised V-ATPase assembly factors, TMEM199 and CCDC115, stabilise HIF1α in aerobic conditions. Rather than preventing the lysosomal degradation of HIF1α, disrupting the V-ATPase results in intracellular iron depletion, thereby impairing PHD activity and leading to HIF activation. Iron supplementation directly restores PHD catalytic activity following V-ATPase inhibition, revealing important links between the V-ATPase, iron metabolism and HIFs. DOI: http://dx.doi. org/10.7554/eLife.22693. 001
Effect of ALDH2 on High Glucose-Induced Cardiac Fibroblast Oxidative Stress, Apoptosis, and Fibrosis

Our study aimed firstly to observe whether ALDH2 was expressed in neonate rat cardiac fibroblasts, then to investigate the effect of activation of ALDH2 on oxidative stress, apoptosis, and fibrosis when cardiac fibroblasts were subjected to high glucose intervention. Cultured cardiac fibroblasts were randomly divided into normal (NG), NG + Alda-1, high glucose (HG), HG + Alda-1, HG + Alda-1 + daidzin, HG + daidzin, and hypertonic groups. Double-label immunofluorescence staining, RT-PCR, and Western blot revealed ALDH2 was expressed in cardiac fibroblasts. Compared with NG, ALDH2 activity and protein expression were reduced, and cardiac fibroblast proliferation, ROS releasing, 4-HNE protein expression, collagen type I and III at mRNA levels, and the apoptosis rate were increased in HG group. While in HG + Alda-1 group, with the increases of ALDH2 activity and protein expression, the cardiac fibroblast proliferation and ROS releasing were decreased, and 4-HNE protein expression, collagen type I and III at mRNA levels, and apoptosis rate were reduced compared with HG group. When treated with daidzin in HG + Alda-1 group, the protective effects were inhibited. Our findings suggested that ALDH2 is expressed in neonate rat cardiac fibroblasts; activation of ALDH2 decreases the HG-induced apoptosis and fibrosis through inhibition of oxidative stress.
A Study to Evaluate the Safety, Tolerability, and Efficacy of Brodalumab in Subjects with Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Objective. To evaluate the efficacy and safety of brodalumab, a human monoclonal antibody inhibitor of the interleukin 17 receptor, in subjects with rheumatoid arthritis (RA). Methods. Patients (n = 252) with inadequate response to methotrexate (MTX) were randomized to receive subcutaneous injections of brodalumab (70 mg, 140 mg, or 210 mg) or placebo. The primary endpoint was the American College of Rheumatology 50% response (ACR50) at Week 12. Results. Demographics and baseline characteristics were generally balanced among treatment groups. At Week 12, ACR50 occurred in 16% (70 mg), 16% (140 mg), 10% (210 mg), and 13% (placebo; all nonsignificant vs placebo) of subjects. No significant treatment effects were observed for the secondary endpoints, including ACR20, ACR70, and Disease Activity Score in 28 joints. Incidences of all adverse events (AE), including serious AE (SAE), were similar across treatment groups. A total of 7 subjects reported SAE during the study (2 in the placebo group and 5 in the brodalumab groups), none of which was treatment related. There was 1 death (cardiopulmonary failure) ∼1 week after the last dose in the 140 mg group. Conclusion. Our study failed to find evidence of meaningful clinical efficacy with brodalumab treatment in subjects with RA who had an inadequate response to MTX. These preliminary results do not support further evaluation of brodalumab as a treatment for RA. Clinicaltrials.gov number: NCT00950989.
Non-classicality and entanglement of symmetric multiqubit states

Quantum vs classical conceptions of nature continue to draw attention from the early days of quantum theory. Understanding decisive quantum features for which no classical explanation exist and their interrelations is of foundational significance. Further, identifying non-classical features is important in information processing tasks as it offers insights as to why quantum protocols outperform their classical counterparts. Here we focus on two illustrious notions of non-classicality: negativity of P phase-space representation and entanglement in symmetric multiqubit systems. We prove that in permutation symmetric multiqubit states and show that non-classicality implies entanglement and vice versa.
Multi-phase transmission for secure cognitive radio networks

In this paper we study secure communications with weak secrecy constraint in a cognitive radio channel, where the secondary receiver is treated as a potential eavesdropper with respect to the primary transmission. The primary's secrecy rate and the transmission scheme should be kept unchanged whether the secondary users transmit or not. We derive the achievable rate of the discrete memoryless multi-phase cognitive channel. To against the information leakage due to the use of Gelfand-Pinsker coding at the secondary transmitter, we derive the corresponding constraints to guarantee the primary's secure transmission. We then specialize the results to the additive white Gaussian noise channels. Numerical results show the advantages of using the proposed multiple-phase transmission scheme over the traditional ones without the additional phase.
Phospholipase Cɛ links G protein-coupled receptor activation to inflammatory astrocytic responses

Neuroinflammation plays a major role in the pathophysiology of diseases of the central nervous system, and the role of astroglial cells in this process is increasingly recognized. Thrombin and the lysophospholipids lysophosphatidic acid and sphingosine 1-phosphate (S1P) are generated during injury and can activate G protein-coupled receptors (GPCRs) on astrocytes. We postulated that GPCRs that couple to Ras homolog gene family, member A (RhoA) induce inflammatory gene expression in astrocytes through the small GTPase responsive phospholipase Cɛ (PLCɛ). Using primary astrocytes from wild-type and PLCɛ knockout mice, we demonstrate that 1-h treatment with thrombin or S1P increases cyclooxygenase 2 (COX-2) mRNA levels ∼10-fold and that this requires PLCɛ. Interleukin-6 and interleukin-1β mRNA levels are also increased in a PLCɛ-dependent manner. Thrombin, lysophosphatidic acid, and S1P increase COX-2 protein expression through a mechanism involving RhoA, catalytically active PLCɛ, sustained activation of protein kinase D (PKD), and nuclear translocation of NF-κB. Endogenous ligands that are released from astrocytes in an in vitro wounding assay also induce COX-2 expression through a PLCɛ- and NF-κB–dependent pathway. Additionally, in vivo stab wound injury activates PKD and induces COX-2 and other inflammatory genes in WT but not in PLCɛ knockout mouse brain. Thus, PLCɛ links GPCRs to sustained PKD activation, providing a means for GPCR ligands that couple to RhoA to induce NF-κB signaling and promote neuroinflammation.
Hubungan Penggunaan Pestisida dan Alat Pelindung Diri dengan Keluhan Kesehatan pada Petani Hortikultura di Buleleng, Bali

Latar belakang dan tujuan: Penggunaan pestisida highly toxic banyak terjadi di negara berkembang termasukIndonesia. Petani Desa Pancasari di Bali merupakan pengguna pestisida aktif, sehingga ada potensi keracunan pestisida.Saat ini belum banyak diketahui perilaku penggunaan pestisida serta alat pelindung diri (APD) dan hubungannyadengan keluhan kesehatan petani di wilayah tersebut.Metode: Survei cross sectional dilakukan pada 87 petani hortikultura. Pengumpulan data dilakukan denganwawancara dan observasi. Data dianalisis secara bivariat dengan chi square test dan multivariat dengan regresi logistikuntuk mengetahui hubungan antara keluhan kesehatan spesifik terkait pestisida (sakit kepala, gatal-gatal, kelelahanmeningkat dan mual) dengan karakteristik sosiodemografi, pengetahuan dan perilaku penggunaan pestisida sertapenggunaan APD.Hasil: Mayoritas petani berumur ? 30 tahun (94,3%), laki-laki (81,6%) dengan pendidikan menengah kebawah (78,2%). Sebanyak 54,1% petani memiliki pengetahuan cukup baik tentang pestisida dan APD, namun perilakunya masih buruk.Sebanyak 60,9% petani memiliki keluhan kesehatan spesifik. Keluhan kesehatan dijumpai berhubungan denganpenggunaan pestisida golongan organophosfat (AOR=3,74; 95%CI: 1,33-10,48), lama hari pemakaian baju kerja sebelumdicuci (AOR=1,37; 95%CI: 1,08-1,75), tidak menggunakan baju panjang pada saat pencampuran (AOR=0,25; 95%CI:0,09-0,76) dan tidak memakai masker pada saat penyemprotan (AOR=0,18; 95%CI: 0,05-0,69). Simpulan: Keluhan kesehatan spesifik pada petani berhubungan dengan penggunaan pestisida golonganorganophosfat, perilaku pemakaian baju kerja dan penggunaan APD yang tidak tepat.
Marked enhancement of lysosomal targeting and efficacy of ErbB2-targeted drug delivery by HSP90 inhibition

Targeted delivery of anticancer drugs to tumor cells using monoclonal antibodies against oncogenic cell surface receptors is an emerging therapeutic strategy. These strategies include drugs directly conjugated to monoclonal antibodies through chemical linkers (Antibody-Drug Conjugates, ADCs) or those encapsulated within nanoparticles that in turn are conjugated to targeting antibodies (Antibody-Nanoparticle Conjugates, ANPs). The recent FDA approval of the ADC Trastuzumab-TDM1 (Kadcyla®; Genentech; San Francisco) for the treatment of ErbB2-overexpressing metastatic breast cancer patients has validated the strong potential of these strategies. Even though the activity of ANPs and ADCs is dependent on lysosomal traffic, the roles of the endocytic route traversed by the targeted receptor and of cancer cell-specific alterations in receptor dynamics on the efficiency of drug delivery have not been considered in these new targeted therapies. For example, constitutive association with the molecular chaperone HSP90 is thought to either retard ErbB2 endocytosis or to promote its recycling, traits undesirable for targeted therapy with ANPs and ADCs. HSP90 inhibitors are known to promote ErbB2 ubiquitination, targeting to lysosome and degradation. We therefore hypothesized that ErbB2-targeted drug delivery using Trastuzumab-conjugated nanoparticles could be significantly improved by HSP90 inhibitor-promoted lysosomal traffic of ErbB2. Studies reported here validate this hypothesis and demonstrate, both in vitro and in vivo, that HSP90 inhibition facilitates the intracellular delivery of Trastuzumab-conjugated ANPs carrying a model chemotherapeutic agent, Doxorubicin, specifically into ErbB2-overexpressing breast cancer cells, resulting in improved antitumor activity. These novel findings highlight the need to consider oncogene-specific alterations in receptor traffic in the design of targeted drug delivery strategies. We suggest that combination of agents that enhance receptor endocytosis and lysosomal routing can provide a novel strategy to significantly improve therapy with ANPs and ADCs.
Mismatch Negativity as a “Translatable” Brain Marker Toward Early Intervention for Psychosis: A Review

Recent reviews and meta-analyses suggest that reducing the duration of untreated psychosis leads to better symptomatic and functional outcome in patients with psychotic disorder. Early intervention attenuates the symptoms of individuals at clinical high-risk (HR) for psychosis and may delay or prevent their transition to psychosis. Identifying biological markers in the early stages of psychotic disorder is an important step toward elucidating the pathophysiology, improving prediction of the transition to psychosis, and introducing targeted early intervention for help-seeking individuals aiming for better outcome. Mismatch negativity (MMN) is a component of event-related potentials that reflects preattentive auditory sensory memory and is a promising biomarker candidate for schizophrenia. Reduced MMN amplitude is a robust finding in patients with chronic schizophrenia. Recent reports have shown that people in the early stages of psychotic disorder exhibit attenuation of MMN amplitude. MMN in response to duration deviants and in response to frequency deviants reveals different patterns of deficits. These findings suggest that MMN may be useful for identifying clinical stages of psychosis and for predicting the risk of development. MMN may also be a “translatable” biomarker since it reflects N-methyl-d-aspartte receptor function, which plays a fundamental role in schizophrenia pathophysiology. Furthermore, MMN-like responses can be recorded in animals such as mice and rats. This article reviews MMN studies conducted on individuals with HR for psychosis, first-episode psychosis, recent-onset psychosis, and on animals. Based on the findings, the authors discuss the potential of MMN as a clinical biomarker for early intervention for help-seeking individuals in the early stages of psychotic disorder, and as a translatable neurophysiological marker for the preclinical assessment of pharmacological agents used in animal models that mimic early stages of the disorder.
Significance of decoy receptor 3 in sera of hepatocellular carcinoma patients

Abstract Objective. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is amplified and over-expressed in various cancers. The objective of the present study was to investigate the concentration of DcR3 in sera of hepatocellular carcinoma (HCC) patients and its clinical significance. Methods. Serum concentrations of DcR3 were measured by enzyme-linked immunosorbent assay (ELISA) in 67 patients with HCC, 8 with liver cirrhosis, 17 with cholecystitis, and in 28 healthy individuals. Immunohistochemistry was employed to access protein expression of DcR3 in the corresponding HCC tissues. Results. Serum concentrations of DcR3 in patients with HCC or cirrhosis were significantly higher than in healthy individuals (P < 0.01). Moreover, serum concentrations of DcR3 in HCC patients were associated with TNM stage, para-cirrhosis, capsular infiltration, and metastasis or recurrence of disease (P < 0.05). There was a positive correlation between the serum concentration of DcR3 and protein expression in HCC tissues (r = 0.472, P < 0.01). Conclusions. The high serum concentration of DcR3 might play a certain role in pathogenesis, progress, and metastasis of HCC. Moreover, DcR3 might serve as a valuable molecular indicator in early diagnosis and contribute to predicting the clinical outcome in HCC patients.
Real-Time Crash Risk Prediction using Long Short-Term Memory Recurrent Neural Network

With the help of traffic detectors widely deployed along arterial roads and intersections, real-time traffic data are collected and updated in a very short time period, which makes it possible to conduct real-time analysis at signalized intersections. Among them, real-time crash risk prediction is one of the most promising and challenging research topics. This study attempts to predict real-time crash risk by considering time series dependency with the employment of a long short-term memory recurrent neural network (LSTM-RNN) algorithm. Also, the synthetic minority over-sampling technique (SMOTE) was utilized in this study to generate a balanced training dataset for algorithm training. In comparison, a conditional logistic model was developed based on matched case control design. Both models were evaluated based on the real-world unbalanced test dataset rather than an artificially balanced dataset. The comparison results indicate that the LSTM-RNN with SMOTE outperforms the conditional logistic model. The methods and findings of this study attempt to verify the feasibility of real-time crash risk prediction by using LSTM-RNN with over-sampled dataset (SMOTE).
The oncogenic T cell LIM‐protein Lmo2 forms part of a DNA‐binding complex specifically in immature T cells

The LIM‐only protein LMO2 is expressed aberrantly in acute T‐cell leukaemias as a result of the chromosomal translocations t(11;14) (p13;q11) or t(7;11) (q35;p13). In a transgenic model of tumorigenesis by Lmo2, T‐cell acute leukaemias arise after an asymptomatic phase in which an accumulation of immature CD4− CD8− double negative thymocytes occurs. Possible molecular mechanisms underlying these effects have been investigated in T cells from Lmo2 transgenic mice. Isolation of DNA‐binding sites by CASTing and band shift assays demonstrates the presence of an oligomeric complex involving Lmo2 which can bind to a bipartite DNA motif comprising two E‐box sequences ∼10 bp apart, which is distinct from that found in erythroid cells. This complex occurs in T‐cell tumours and it is restricted to the immature CD4− CD8− thymocyte subset in asymptomatic transgenic mice. Thus, ectopic expression of Lmo2 by transgenesis, or by chromosomal translocations in humans, may result in the aberrant protein interactions causing abnormal regulation of gene expression, resulting in a blockage of T‐cell differentiation and providing precursor cells for overt tumour formation.