Miracle-dz/UniFAR-FTUs huggingface dataset:
First report of Enterobacter cloacae as a causative agent of soft rot disease in dragon fruit (Hylocereus undatus) stems in Peru

The objective of the present research was to identify the causal agent of soft rot disease in the stems of pitahaya plants (Hylocereus undatus (Haw.) Britton & Rose), also known as dragon fruit, in two production areas of Peru. Typical symptoms observed include rotting and soft consistency in stems, as well as yellowish colourations, which usually begin at the tips and outer edges of the stems and extend until they are completely decomposed. Symptomatic samples of pitahaya stalks were collected from two commercial fields, the first from the district of Independencia, Pisco, Ica, and the second from the district of Naranjos, Rioja, San Martin. The collected samples were transferred to the phytopathology laboratory of the National Agrarian University – La Molina where 19 bacterial colonies isolated from symptomatic stem tissue were processed. Nine bacterial colonies were selected from the initial 19 for further analysis. The nine selected colonies were gram negative, positive for the catalase enzyme, negative for the enzyme oxidase, and positive for pectinase production, which causes soft rot in potato tubers. These results indicated that these isolates correspond to the Enterobacteriaceae family. According to molecular tests and analysis of the 16s region of ribosomal DNA, all bacteria corresponded to a single taxonomic genus, Enterobacter. This bacterium presented a 99.85% homology with Enterobacter cloacae (accession number MH788982.1). The sequences from the nine selected isolates were entered into GenBank under accession number MN784371. In the pathogenicity test, 100% infection was obtained in the pitahaya stems and plants inoculated with E. cloacae, and the symptomatology that developed was the same as that observed in the two fields from where the samples were collected. Given these results, it can be concluded that E. cloacae is a causative agent of soft rot disease of the stems of H. undatus in the districts of Independencia and Naranjos, and this is also the first report of this bacterium as a pathogen of pitahaya in Peru.
The efficacy of mometasone furoate for children with asthma: a meta-analysis of randomized controlled trials

Introduction The influence of mometasone furoate for paediatric asthma remains controversial. Aim We conducted a systematic review and meta-analysis to explore the efficacy and safety of mometasone furoate for paediatric asthma. Material and methods We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through October 2019 for randomized controlled trials assessing the effect of mometasone furoate versus placebo for paediatric asthma. This meta-analysis was performed using the random-effects model. Results Four RCTs were included in the meta-analysis. Overall, as compared to placebo for paediatric asthma, mometasone furoate is associated with substantially increased predicted forced expiratory volume in 1 s (FEV1) (mean difference (MD) = 7.53; 95% CI: 7.02–8.04; p < 0.00001), FEV1 (MD = 0.11; 95% CI: 0.10–0.12; p < 0.00001), and morning peak expiratory flow (AM PEF) (MD = 17.70; 95% CI: 9.91–25.49; p < 0.00001), but demonstrates no obvious effect on pharyngitis (RR = 0.96; 95% CI: 0.59–1.58; p = 0.89), upper respiratory tract infections (RR = 0.73; 95% CI: 0.50–1.05; p = 0.09), or adverse events (RR = 1.05; 95% CI: 0.84–1.31; p = 0.69). Conclusions Mometasone furoate may be effective and safe for paediatric asthma.
Good mathematics teaching at lower primary school level

This paper explores Norwegian lower primary teachers’ views about good mathematics teaching as revealed in a focus group interview at the end of a two-year school-based professional development program. Analyses of the empirical data indicate three main categories of findings: the teachers’ facilitation of learning, the students’ thinking in and about mathematics and the use of teaching aids in teaching. The results are discussed in relation to other Nordic studies and possible implications are also provided.
Mitigating the Persistent Effects of Early-Life Shocks: Evidence from Safety Net Programs in Colombia

Although the early-origins literature in economics and other disciplines suggests that early-life shocks have long-term consequences, it does not investigate whether later human capital investments have the potential to mitigate such consequences. This study examines how early-life conditions interact with subsequent human capital investments to influence future educational outcomes. To provide causal evidence, we exploit two sources of exogenous variation: i) variation in early-life environments resulting from a child’s exposure to extreme rainfall and drought shocks in early-life; and ii), variation in subsequent investments resulting from the availability of conditional cash transfers (CCT) that promote investments in children’s health and education. Using Colombian administrative data, we combine a natural experiment with a regression discontinuity design using the CCT assignment rule. Results show that although the CCT has an overall positive impact on children’s educational outcomes that is robust to accounting for exposure to negative shocks early in life, there is limited evidence that the CCT has a differential effect on children exposed to early shocks. However, the main effect of the CCT is large enough to offset the negative impact of the weather shock. These findings have important policy implications as they provide evidence of the role of social policies in closing gaps generated by early-life trauma.
Response to opioids is dependent on sociability levels

Social environment influences the trajectory of developing opioid use disorder (OUD). Thus, the present study tested the hypothesis that sociability levels will affect the responses to opioids. Mice were tested for their baseline sociability, anxiety levels, pain sensitivities, and their acute locomotor response to 5 mg/kg opioids. Then, they were administered repeatedly with saline, hydrocodone, or morphine (20 mg/kg for 5 days, and then 40 mg/kg for 5 days). Subsequently, they were examined for the expression of locomotor sensitization and retested for the effects of opioids on their sociability, anxiety levels, and pain sensitivity. On the basis of their baseline sociability level, mice were divided into socially avoiding and socially exploring. Socially avoiding and socially exploring mice did not differ in their baseline weight and anxiety sensitivities. Socially avoiding mice had slightly higher baseline heat sensitivity than those in socially exploring mice. Repeated administration of opioids had differential effects in socially avoiding and socially exploring mice. In both social groups, repeated morphine administration had overall stronger effects compared with hydrocodone. Morphine-treated socially exploring mice developed greater locomotor sensitization than those in morphine-treated socially avoiding mice. Morphine-treated socially avoiding mice, but not socially exploring mice, spent more time in the center zone of the open-field test and in the light zone of light/dark boxes, and developed heat hyperalgesia. This study suggests that socially exploring animals are more sensitive to the sensitizing effects of opioids. In contrast, opioids have greater effects on the stress and pain systems of socially avoiding animals. Thus, the underlying mechanisms for developing OUD might differ in individuals with various sociability levels.
Sonic hedgehog is expressed in human brain arteriovenous malformations and induces arteriovenous malformations in vivo

Abnormalities in arterial versus venous endothelial cell identity and dysregulation of angiogenesis are deemed important in the pathophysiology of brain arteriovenous malformations (AVMs). The Sonic hedgehog (Shh) pathway is crucial for both angiogenesis and arterial versus venous differentiation of endothelial cells, through its dual role on the vascular endothelial growth factor/Notch signaling and the nuclear orphan receptor COUP-TFII. In this study, we show that Shh, Gli1 (the main transcription factor of the Shh pathway), and COUP-TFII (a target of the non-canonical Shh pathway) are aberrantly expressed in human brain AVMs. We also show that implantation of pellets containing Shh in the cornea of Efnb2/LacZ mice induces growth of distinct arteries and veins, interconnected by complex sets of arteriovenous shunts, without an interposed capillary bed, as seen in AVMs. We also demonstrate that injection in the rat brain of a plasmid containing the human Shh gene induces the growth of tangles of tortuous and dilated vessels, in part positive and in part negative for the arterial marker αSMA, with direct connections between αSMA-positive and -negative vessels. In summary, we show that the Shh pathway is active in human brain AVMs and that Shh-induced angiogenesis has characteristics reminiscent of those seen in AVMs in humans.
Plasma NRTI concentration and their associations with liver and renal parameters in people living with HIV.

: Associations between markers of liver and renal dysfunction and NRTI plasma exposure are ill-defined. As part of a large cohort study (POPPY), we analysed associations between ALT and eGFR results in people living with HIV on tenofovir (TFV) disoproxil fumarate (TDF), emtricitabine (FTC), abacavir (ABC) and lamivudine (3TC). While we found no associations between NRTI concentrations and ALT, lower eGFR values were associated with greater TFV, FTC and 3TC exposure, whereas ABC showed no associations.
Analysis of Quasi-Zenith Satellite System Signal Acquisition and Multiplexing Characteristics in China Area

On the basis of realizing regional navigation, the Quasi-Zenith Satellite System (QZSS) has advanced navigation function, which leads to the broadcasting of more signals in a single frequency of QZSS signals. Current signal transmission technology cannot solve this problem, so it is necessary to design a signal multiplexing method. The current QZSS satellite interface document does not disclose the multiplexing modulation method of the signal transmission, which has a certain impact on the acquisition of high-precision observation data and further data processing. The iGMAS (International GNSS Monitoring & Assessment System) Monitoring and Evaluation Center of the 54th Research Institute of China Electronics Technology Group Corporation has used the low-distortion data acquisition and processing platform and refined signal software receiving processing algorithm of the iGMAS to complete the signal acquisition and analysis of QZSS satellites. Analysis of the multiplexing and modulation method and signal characteristics for the QZSS has been carried out, which can provide a reference for the design and data processing of high-precision receivers.
Antiretroviral Therapy Concentrations Differ in Gut vs. Lymph Node Tissues and Are Associated With HIV Viral Transcription by a Novel RT-ddPCR Assay.

BACKGROUND Most HIV-infected cells during antiretroviral therapy (ART) persist in lymphoid tissues. Studies disagree on whether suboptimal tissue ART concentrations contribute to ongoing HIV replication during viral suppression. METHODS We performed a cross-sectional study in virally-suppressed HIV+ participants measuring lymphoid tissue ART [darunavir (DRV), atazanavir (ATV), and raltegravir (RAL)] concentrations by LC-MS/MS assay. Tissue and plasma ART concentrations were used to estimate TPRs and drug-specific tissue:inhibitory concentration ratios (TICs). HIV DNA and sequentially produced HIV RNA transcripts were quantified from rectal biopsies using droplet digital PCR (ddPCR) assays. RESULTS Tissue samples were collected in duplicate from 19 participants: 38 rectal, 8 ileal (4 RAL, 2 DRV, 2 ATV), and 6 lymph node (4 RAL, 2 DRV) samples. Overall, median TICs were higher for RAL than DRV or ATV (both P = 0.006). Median TICs were lower in lymph nodes vs. ileum (0.49 vs. 143, P = 0.028) or rectum (33, P = 0.019), and all ART levels were below target concentrations. Higher rectal TICs were associated with lower HIV RNA transcripts (read-through, long LTR, and Nef, P all < 0.026) and a lower long LTR RNA/long LTR DNA ratio (P = 0.021). CONCLUSIONS We observed higher tissue ART concentrations in ileum and rectum compared with lymph nodes. We observed higher HIV transcription in participants with lower rectal ART concentrations. These findings add to the limited data supporting the idea that viral transcription may be influenced by ART concentrations in lymphoid tissues. Further exploration of tissue pharmacokinetics is needed in future HIV eradication strategies.
MK2 Inhibition Induces p53-Dependent Senescence in Glioblastoma Cells

MAPK-activated protein kinase 2 (MK2) has diverse roles in cancer. In response to chemotherapy, MK2 inhibition is synthetically lethal to p53-deficiency. While TP53 deletion is rare in glioblastomas, these tumors often carry TP53 mutations. Here, we show that MK2 inhibition strongly attenuated glioblastoma cell proliferation through p53wt stabilization and senescence. The senescence-inducing efficacy of MK2 inhibition was particularly strong when cells were co-treated with the standard-of-care temozolomide. However, MK2 inhibition also increased the stability of p53 mutants and enhanced the proliferation of p53-mutant stem cells. These observations reveal that in response to DNA damaging chemotherapy, targeting MK2 in p53-mutated cells produces a phenotype that is distinct from the p53-deficient phenotype. Thus, MK2 represents a novel drug target in 70% glioblastomas harboring intact TP53 gene. However, targeting MK2 in tumors with TP53 mutations may accelerate disease progression. These findings are highly relevant since TP53 mutations occur in over 50% of all cancers.
Cold agglutinin-associated B-cell lymphoproliferative disease shows highly recurrent gains of chromosome 3 and 12 or 18.

Primary cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by a distinct type of B-cell lymphoproliferative disease of the bone marrow. 1,2 We have recently evaluated the use of bendamustine-rituximab therapy for CAD and found that B cell – directed therapy is highly efficient and safe and may be considered first line therapy for relatively fit patients with CAD. 3 Hemolysis is mediated by binding of monoclonal immunoglobulin M antibodies (cold agglutinins) to the erythrocyte surface I antigen at temperatures below central body temperature, followed by agglutination and complement classical pathway activation. 1,4 Immunoglobulins are almost exclusively encoded by heavy chain variable gene IGHV4-34 and mostly by k light chain variable gene IGKV3-20 or similar IGHV3-15 . 5 We recently revealed recurrent KMT2D and CARD11 gene mutations in CAD-associated B-cell lymphoproliferative disease. 6 Chromosome instability is one of the hallmarks of cancer, and it has implications in disease diagnostics, prognostics, and response to therapy. Copy number variations (CNVs), a gain or loss of copies of DNA segments larger than 1
Rapid Microwave-Assisted Cisplatin-Loaded Solid Lipid Nanoparticles: Synthesis, Characterization and Anticancer Study

Cisplatin is one of the most leading potent chemotherapy drugs prescribed for the treatment of most solid tumors. However, the induction of toxicities and the development of resistance restricts its applications. Efforts are made in the proposed study to control the delivery of cisplatin to tumor sites by incorporating it into solid lipid nanoparticle (SLNs) drug carriers. By considering this fact, in the current research work, a single-step, one-pot, microwave-assisted technology was used to produce cisplatin-loaded SLNs. The shape of the SLNs was observed to be spherical, with a uniform size distribution of 74.85 nm, polydispersity index (PDI) of 0.311, and zeta potential of −20.8 mV. The percentage of encapsulation efficiency was found to be 71.85%. In vitro drug release study was calculated to be 80% in 24 h. The formulation in blood was found to be safe; a study of hemolysis confirmed this. Breast cancer cell line MCF-7 was used to test cytotoxicity and cellular interaction of cisplatin-loaded SLNs with an IC50 value of 6.51 ± 0.39 μg/mL. Overall, the results of our findings show that the approach of SLNs-based, cisplatin-based, drug delivery has led to increased sustainability in breast cancer therapy with superior biocompatibility.
Allosteric coupling between Mn2+ and dsDNA controls the catalytic efficiency and fidelity of cGAS

Abstract Cyclic-G/AMP (cGAMP) synthase (cGAS) triggers host innate immune responses against cytosolic double-stranded (ds)DNA arising from genotoxic stress and pathogen invasion. The canonical activation mechanism of cGAS entails dsDNA-binding and dimerization. Here, we report an unexpected activation mechanism of cGAS in which Mn2+ activates monomeric cGAS without dsDNA. Importantly, the Mn2+-mediated activation positively couples with dsDNA-dependent activation in a concerted manner. Moreover, the positive coupling between Mn2+ and dsDNA length-dependent activation requires the cognate ATP/GTP substrate pair, while negative-cooperativity suppresses Mn2+ utilization by either ATP or GTP alone. Additionally, while Mn2+ accelerates the overall catalytic activity, dsDNA length-dependent dimerization specifically accelerates the cyclization of cGAMP. Together, we demonstrate how the intrinsic allostery of cGAS efficiently yet precisely tunes its activity.
A TDM-Based 16-Channel AFE ASIC With Enhanced System-Level CMRR for Wearable EEG Recording With Dry Electrodes

A multi-channel analog front-end (AFE) ASIC for wearable EEG recording application is presented in this article. Two techniques, namely chopping stabilization (CS) and time-division-multiplexing (TDM) are combined in a unified manner to improve the input-referred noise and the system level common-mode rejection ratio (CMRR) for multi-channel AFE. With the proposed TDM/CS structure, multiple channels can share single second-stage amplifier for significant reduction in chip size and power consumption. Dual feedback loops for input impedance boosting as well as electrode offset cancellation are incorporated in the system. Implemented in a 0.18-μm CMOS process, the AFE consumes 24 μW under 1 V supply. The input referred noise is 0.63 μVrms in 0.5 Hz–100 Hz and the input impedance is boosted to 560 MΩ at 50 Hz. The measured amplifier intrinsic CMRR and system-level AFE CMRR are 89 dB and 82 dB, respectively.
Inclusion of actuator dynamics in simulations of assisted human movement

Simulation of musculoskeletal systems using dynamic optimization is a powerful approach for studying the biomechanics of human movements and can be applied to human‐robot interactions. The simulation results of human movements augmented by robotic devices may be used to evaluate and optimize the device design and controller. However, simulations are limited by the accuracy of the models which are usually simplified for computation efficiency. Typically, the powered robotic devices are often modeled as massless, ideal torque actuators that is without mass and internal dynamics, which may have significant impacts on the simulation results. This article investigates the effects of including the mass and internal dynamics of the device in simulations of assisted human movement. The device actuator was modeled in various ways with different detail levels. Dynamic optimization was used to find the muscle activations and actuator commands in motion tracking and predictive simulations. The results showed that while the effects of device mass and inertia can be small, the electrical dynamics of the motor can significantly impact the results. This outcome suggests the importance of using an accurate actuator model in simulations of human movement augmented by assistive devices.
Spontaneous and emergent extrapyramidal syndromes in Black Africans with first-episode schizophrenia and first exposure to antipsychotics

Abstract Background Persons of African ancestry are thought to carry a higher risk for extrapyramidal syndromes (EPS) in schizophrenia. Aim We investigated the phenomenon of spontaneous and treatment-emergent EPS in a sample comprising Xhosa (South Africa) and Yoruba (Nigeria) Africans with first-episode schizophrenia and first exposure to antipsychotics. Methods The Extrapyramidal Symptom Rating Scale (ESRS) and a variety of validated tools were used for the assessment of participants before, and two-weekly after treatment with low dose flupenthixol decanoate. Participants were followed up for 12 months. Association of EPS with clinical characteristics was investigated using Pearson’s correlation and linear regression analyses. Results Of 88 participants at baseline, 16 (18.1%) had at least one definite EPS prior to antipsychotic exposure and 34 (38.6%) had treatment-emergent EPS. While spontaneous Parkinsonism was associated with negative symptoms (r = 0.2, p = 0.043; β = 0.6, p = 0.043), treatment-emergent EPS demonstrated non-significant correlations with clinical characteristics. Apart from dyskinesia, the frequency of treatment-emergent EPS decreased over 12 months observation. Conclusion These findings support the hypothesis suggesting that spontaneously occurring Parkinsonism in schizophrenia may be the motor spectrum of negative symptomatology. Future studies of this relationship may lead to early identification of patients who may be more sensitive to EPS.
Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): Primary analysis of IMvigor210 cohort 1.

LBA4500Background: Cisplatin-based chemo is a standard 1L treatment (tx) for mUC and the only tx that prolongs OS; however, age or comorbidities render many pts ineligible, and 30-50% receive no tx. Atezo (MPDL3280A) is active and well tolerated in platinum-treated mUC, justifying testing atezo as 1L tx in cisplatin-ineligible pts. Methods: Pts were chemo naive in the metastatic setting and cisplatin ineligible (renal [GFR > 30 but < 60 mL/min]/hearing impairment, ≥ G2 peripheral neuropathy [PN] or ≥ ECOG PS2). Atezo 1200 mg was given IV q3w until PD (RECIST v1.1). Centrally assessed PD-L1 on tumor infiltrating immune cells (IC; SP142 IHC assay) was scored IC2/3, 1 or 0. The primary efficacy endpoint was confirmed ORR assessed per RECIST v1.1 (central independent review facility) using a data cutoff of Sep 14, 2015. Results: 119 efficacy/safety-evaluable pts of any PD-L1 IC had a median age of 73 y: 21% ≥ 80 y. 18% had prior systemic tx (21% [neo]adjuvant); 10% had radiotherapy. 66% had visceral mets. 71%.
Nα-Acetylation of the virulence factor EsxA is required for mycobacterial cytosolic translocation and virulence

The Mycobacterium tuberculosis virulence factor EsxA and its chaperone EsxB are secreted as a heterodimer (EsxA:B) and are crucial for mycobacterial escape from phagosomes and cytosolic translocation. Current findings support the idea that for EsxA to interact with host membranes, EsxA must dissociate from EsxB at low pH. However, the molecular mechanism by which the EsxA:B heterodimer separates is not clear. In the present study, using liposome-leakage and cytotoxicity assays, LC-MS/MS–based proteomics, and CCF-4 FRET analysis, we obtained evidence that the Nα-acetylation of the Thr-2 residue on EsxA, a post-translational modification that is present in mycobacteria but absent in Escherichia coli, is required for the EsxA:B separation. Substitutions at Thr-2 that precluded Nα-acetylation inhibited the heterodimer separation and hence prevented EsxA from interacting with the host membrane, resulting in attenuated mycobacterial cytosolic translocation and virulence. Molecular dynamics simulations revealed that at low pH, the Nα-acetylated Thr-2 makes direct and frequent “bind-and-release” contacts with EsxB, which generates a force that pulls EsxB away from EsxA. In summary, our findings provide evidence that the Nα-acetylation at Thr-2 of EsxA facilitates dissociation of the EsxA:B heterodimer required for EsxA membrane permeabilization and mycobacterial cytosolic translocation and virulence.