Miracle-dz/UniFAR-FTUs huggingface dataset:
Hybrid time-domain and continuous-wave diffuse optical tomography instrument with concurrent, clinical magnetic resonance imaging for breast cancer imaging

Abstract. Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow. The instrument is described in detail here. Image reconstructions of a tissue phantom are presented as an initial indicator of the system’s ability to accurately reconstruct optical properties and the concrete benefits of the spatial constraints provided by concurrent MRI. Last, we briefly discuss how various data combinations that the instrument could facilitate, including tissue perfusion, can enable more comprehensive assessment of lesion physiology.
Rebooting resilience: shifts toward dynamic, multi-level, and technology-based approaches for people living with HIV

ABSTRACT Resilience research has often been characterized by a static conceptualization of resilience that focuses on individual-level factors that help people living with HIV (PLHIV) adapt to HIV-related challenges and overcome other life adversities. Early conceptualizations often depicted resilience as a static, stable construct, with limited attention paid to the social context and broader systems that may foster or discourage resilient adaptation across time and place. This special issue seeks to challenge these conventional views by highlighting innovative HIV resilience research across the globe. Far from ignoring socio-cultural contexts, studies presented in this issue directly address systemic stigma and discrimination against PLHIV, as well as sexual and gender minority individuals, and identify unique opportunities to promote resilience through building strong “villages” (i.e., social networks), reducing structural inequities, and enhancing HIV treatment and care systems. In addition, papers included in this issue address the promise and challenges of utilizing mobile Heath (mHealth) technology to build resilience for PLHIV through improving psychosocial and clinical outcomes.
New Viruses from the Ectoparasite Mite Varroa destructor Infesting Apis mellifera and Apis cerana

Varroa destructor is an ectoparasitic mite of Asian or Eastern honeybees Apis cerana (A. cerana) which has become a serious threat to European subspecies of Western honeybees Apis mellifera (A. mellifera) within the last century. V. destructor and its vectored honeybee viruses became serious threats for colony survival. This is a short period for pathogen- and host-populations to adapt. To look for possible variation in the composition of viral populations we performed RNA metagenomic analysis of the Western honeybee subspecies A. m. ligustica, A. m. syriaca, A. m. intermissa, and A. cerana and their respective V. destructor mites. The analysis revealed two novel viruses: Varroa orthomyxovirus-1 (VOV-1) in A. mellifera and V. destructor and a Hubei like-virga virus-14 homolog in V. destructor. VOV-1 was more prevalent in V. destructor than in A. mellifera and we found evidence for viral replication in both hosts. Interestingly, we found differences in viral loads of A. cerana and their V. destructor, A. m. intermissa, and its V. destructor showed partial similarity, while A. m. ligustica and A. m. syriaca and their varroa where very similar. Deformed wing virus exhibited 82.20%, 99.20%, 97.90%, and 0.76% of total viral reads in A. m. ligustica, A. m. syriaca, A. m. intermissa, and A. cerana, respectively. This is the first report of a complete segmented-single-stranded negative-sense RNA virus genome in honeybees and V. destructor mites.
Medium Chain Carboxylic Acids from Complex Organic Feedstocks by Mixed Culture Fermentation

Environmental pressures caused by population growth and consumerism require the development of resource recovery from waste, hence a circular economy approach. The production of chemicals and fuels from organic waste using mixed microbial cultures (MMC) has become promising. MMC use the synergy of bio-catalytic activities from different microorganisms to transform complex organic feedstock, such as by-products from food production and food waste. In the absence of oxygen, the feedstock can be converted into biogas through the established anaerobic digestion (AD) approach. The potential of MMC has shifted to production of intermediate AD compounds as precursors for renewable chemicals. A particular set of anaerobic pathways in MMC fermentation, known as chain elongation, can occur under specific conditions producing medium chain carboxylic acids (MCCAs) with higher value than biogas and broader applicability. This review introduces the chain elongation pathway and other bio-reactions occurring during MMC fermentation. We present an overview of the complex feedstocks used, and pinpoint the main operational parameters for MCCAs production such as temperature, pH, loading rates, inoculum, head space composition, and reactor design. The review evaluates the key findings of MCCA production using MMC, and concludes by identifying critical research targets to drive forward this promising technology as a valorisation method for complex organic waste.
Understanding nitrogen recovery from wastewater with a high nitrogen concentration using microbial electrolysis cells

Abstract This study was aimed at understanding the effect of applied voltage, catholyte and reactor scale on nitrogen recovery from two different organic wastes (digestate and pig slurry) by means of microbial electrolysis cell (MEC) technology. For this purpose, MEC sizes of 100, 500 and 1000 mL were tested at applied voltages of 0.6, 1 and 1.4 V using either a phosphate-buffered solution or NaCl solution as the catholyte. By increasing the reactor size from 500 to 1000 mL, a decrease in the ammonia recovery efficiency from 47 to 42% was observed. The results also showed that the phosphate-buffered solution is preferable as the catholyte and that the voltage applied does not have a noticeable effect on current production and ammonia recovery. Low biodegradability of the wastes was identified as the main bottleneck.
Identification and Characterization of Rhizoctonia Species Associated with Soybean Seedling Disease.

In an effort to identify the Rhizoctonia spp. associated with seedling diseases of soybean, Rhizoctonia isolates were recovered from soybean seedlings with damping off and root and hypocotyl rot symptoms from Arkansas, Illinois, Kansas, Michigan, Minnesota, and the Canadian province of Ontario between 2012 and 2014. Based on cultural morphology, polymerase chain reaction restriction fragment length polymorphism, and phylogenetic analysis of the internal transcribed spacer (ITS) region of the ribosomal RNA genes, 80 isolates were confirmed to be Rhizoctonia solani, 24 were binucleate Rhizoctonia spp. , and 10 were R. zeae. Of the 80 R. solani isolates, one belonged to anastomosis group (AG) 2-1, 52 belonged to AG-2-2IIIB, five belonged to AG-3 PT, three belonged to AG-4 HGI, two belonged to AG-4 HGIII, nine belonged to AG-7, and eight belonged to AG-11. Bayesian inference of phylogeny using the ITS region revealed two clades of R. solani AG-7 that possibly correspond to different AG-7 subgroups. Phylogenetic analysis also provided evidence for genetic relatedness between certain binucleate Rhizoctonia and some R. solani isolates. On 'Williams 82' soybean, isolates of AG-2-2IIIB were the most aggressive, followed by isolates of AG-7, AG-4, and AG-11. On 'Jubilee', a sweet corn cultivar, AG-2-2IIIB and AG-4 isolates caused significant stunting and root damage, whereas the damage caused by the AG-11 isolates was mostly restricted to the mesocotyl. Isolates of R. zeae and the binucleate Rhizoctonia spp. were not pathogenic on soybean or corn. Our results indicate that soybean and corn are hosts to the predominant and aggressive AG of R. solani, implying that rotation between these two crops may not be an effective management practice.
Proteomic and Phosphoproteomic Analysis in Tobacco Mosaic Virus-Infected Tobacco (Nicotiana tabacum)

Tobacco mosaic virus (TMV) is a common source of biological stress that significantly affects plant growth and development. It is also useful as a model in studies designed to clarify the mechanisms involved in plant viral disease. Plant responses to abiotic stress were recently reported to be regulated by complex mechanisms at the post-translational modification (PTM) level. Protein phosphorylation is one of the most widespread and major PTMs in organisms. Using immobilized metal ion affinity chromatography (IMAC) enrichment, high-pH C18 chromatography fraction, and high-accuracy mass spectrometry (MS), a set of proteins and phosphopeptides in both TMV-infected tobacco and control tobacco were identified. A total of 4905 proteins and 3998 phosphopeptides with 3063 phosphorylation sites were identified. These 3998 phosphopeptides were assigned to 1311 phosphoproteins, as some proteins carried multiple phosphorylation sites. Among them, 530 proteins and 337 phosphopeptides corresponding to 277 phosphoproteins differed between the two groups. There were 43 upregulated phosphoproteins, including phosphoglycerate kinase, pyruvate phosphate dikinase, protein phosphatase 2C, and serine/threonine protein kinase. To the best of our knowledge, this is the first phosphoproteomic analysis of leaves from a tobacco cultivar, K326. The results of this study advance our understanding of tobacco development and TMV action at the protein phosphorylation level.
First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors

PF‐06647263, a novel antibody–drug conjugate consisting of an anti‐EFNA4 antibody linked to a calicheamicin payload, has shown potent antitumor activity in human xenograft tumor models, including triple‐negative breast cancer (TNBC). In the dose‐escalation part 1 of this multicenter, open‐label, phase I study (NCT02078752), successive cohorts of patients (n, 48) with advanced solid tumors and no available standard therapy received PF‐06647263 every 3 weeks (Q3W) or every week (QW), following a modified toxicity probability interval (mTPI) method (initial dosing: 0.015 mg/kg Q3W). Primary objective in part 1 was to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D). In part 2 (dose‐expansion cohort), 12 patients with pretreated, metastatic TNBC received PF‐06647263 at the RP2D to further evaluate tumor response and overall safety. PF‐06647263 QW administration (n, 23) was better tolerated than the Q3W regimen (n, 25) with only 1 DLT reported (thrombocytopenia). The most common AEs with the QW regimen (fatigue, nausea, vomiting, mucosal inflammation, thrombocytopenia, and diarrhea) were mostly mild to moderate in severity. The MTD was not estimated. PF‐06647263 exposures increased in a dose‐related manner across the doses evaluated. The RP2D was determined to be 0.015 mg/kg QW. Six (10%) patients achieved a confirmed partial response and 22 (36.7%) patients had stable disease. No correlations were observed between tumor responses and EFNA4 expression levels. Study findings showed manageable safety and favorable PK for PF‐06647263 administered QW at the RP2D, with preliminary evidence of limited antitumor activity in patients with TNBC and ovarian cancer.
The effects of bifenthrin and temperature on the endocrinology of juvenile Chinook salmon

The San Francisco Bay delta (USA) is experiencing seasonally warmer waters attributable to climate change and receives rainstorm runoff containing pyrethroid pesticides. Chinook salmon (Oncorhynchus tshawytscha) inhabit the affected waterways from hatch through smoltification, and thus juvenile fish may experience both pyrethroid and warmer water exposures. The effects of higher temperatures and pesticide exposure on presmolt Chinook are unknown. To improve understanding of the potential interaction between temperature and pesticide exposure on salmonid development, juvenile alevin and fry were reared in 11, 16.4, and 19 °C freshwater for 11 d and 2 wk, respectively, and exposed to nominal concentrations of 0, 0.15, and 1.5 µg/L bifenthrin for the final 96 h of rearing. Estradiol‐17β (E2), testosterone, triiodothyronine, and thyroxine levels were measured in whole‐body homogenates using hormone‐specific enzyme‐linked immunosorbent assays. Brain gonadotropin‐releasing hormone receptor (GnRH2), dopamine receptor 2A, and growth hormone 1 (GH1) mRNA levels were measured using quantitative PCR. Results showed significantly decreased survival and condition factors observed with increasing temperature in alevin. Alevin thyroid hormones increased significantly with temperature, but fry thyroid hormones trended toward a decrease at lower temperatures with increasing bifenthrin exposure. There were significant reductions in fry testosterone and E2 at 11 °C with increasing bifenthrin treatments and significant changes in GnRH2 and GH1 gene expression in both alevin and fry, indicating potential disruption of hormonal and signaling pathways. Environ Toxicol Chem 2019;38:852–861. © 2019 SETAC
Tissue-Specific Transcriptome Analysis Reveals Candidate Genes for Terpenoid and Phenylpropanoid Metabolism in the Medicinal Plant Ferula assafoetida

Ferula assafoetida is a medicinal plant of the Apiaceae family that has traditionally been used for its therapeutic value. Particularly, terpenoid and phenylpropanoid metabolites, major components of the root-derived oleo-gum-resin, exhibit anti-inflammatory and cytotoxic activities, thus offering a resource for potential therapeutic lead compounds. However, genes and enzymes for terpenoid and coumarin-type phenylpropanoid metabolism have thus far remained uncharacterized in F. assafoetida. Comparative de novo transcriptome analysis of roots, leaves, stems, and flowers was combined with computational annotation to identify candidate genes with probable roles in terpenoid and coumarin biosynthesis. Gene network analysis showed a high abundance of predicted terpenoid- and phenylpropanoid-metabolic pathway genes in flowers. These findings offer a deeper insight into natural product biosynthesis in F. assafoetida and provide genomic resources for exploiting the medicinal potential of this rare plant.
Variable sources of Bk virus in renal allograft recipients

BK virus is the causative agent of polyomavirus‐associated nephropathy, a major cause of kidney transplant failure affecting 1%‐10% of recipients. Previous studies that investigated the viral source on the kidney recipient pointed that the donor is implicated in the origin of human polyomavirus BK (BKPyV) infection in recipients, but giving the low genetic variability of BKPyV this subject is still controversial. The aim of this study was to determine if BKPyV replicating in kidney recipients after transplantation is always originated from the donor. Urine and blood samples from 68 pairs of living donors and kidney recipients who underwent renal transplantation from August 2010‐September 2011 were screened for BKPyV by real time polymerase chain reaction. Only three recipients presented viremia. When both donors and recipients were BKPyV positive, a larger fragment of VP1 region was obtained and sequenced to determine the level of similarity between them. A phylogenetic tree was built for the 12 pairs of sequences obtained from urine and high level of similarity among all sequences was observed, indicating that homology inferences for donor and recipient viruses must be cautiously interpreted. However, a close inspection on the donor‐recipient pairs sequences revealed that 3 of 12 pairs presented considerably different viruses and 4 of 12 presented mixed infection, indicating that the source of BKPyV infection is not exclusively derived from the donor. We report that about 60% of the renal recipients shed BKPyV genetically distinct from the donor, confronting the accepted concept that the donor is the main source of recipients’ infection.
Relief from incidental fear evokes exuberant risk taking

Incidental emotions are defined as feelings that are unrelated to a decision task at hand and thereby not normatively relevant for making choices. The precise influence and formal theoretical implications of incidental emotions regarding financial risk taking are still largely unclear. An effect of incidental emotion on decision-making would challenge the main extant formal theoretical economic models because such models do not allow for an effect of incidental emotions. As financial risk taking is pervasive in modern economies, the role of incidental emotions is an important issue. The goal of this experimental study is threefold. First, we examine the impact of incidental fear on the choice between a sure and a risky monetary option. A well-validated method of fear induction, using electric shocks, is employed for that purpose. Based on emotion studies we hypothesize less risk taking under fear and more risk taking when relieved of fear. Our second goal is to investigate the relative performance of the main existing formal theoretical economic models (based on Expected Utility Theory, Prospect Theory, or the Mean-Variance model) in explaining the behavioral data. We also investigate how these models can be adjusted to accommodate any observed influence of incidental emotion. For that reason, we first theoretically model the potential pathways of incidental fear (and the relief thereof) via the valuation of the choice option rewards or risk-assessment. We then estimate the relevant parameters allowing for both additive as well as interactive effects. Our third and final goal is to explore the neural basis of any observed influence of incidental emotions on decision-making by means of a model-based fMRI analysis, using the findings of existing neuroeconomic studies as the basis for our hypotheses. Our results indicate that the relief of fear can give a substantial boost to financial risk taking (suggestive of exuberance). This impact is best captured by Prospect Theory if we allow for an increase in participants’ valuation of option outcomes when relieved of fear. Moreover, this impact is manifested at the neural level by the activity of the ventromedial prefrontal cortex (vmPFC), a brain area widely regarded as being central for valuation.
Oxidase or peptidase? A computational insight into a putative aflatoxin oxidase from Armillariella tabescens

Aflatoxin oxidase (AFO), an enzyme isolated from Armillariella tabescens, has been reported to degrade aflatoxin B1 (AFB1). However, recent studies reported sequence and structure similarities with the dipeptidyl peptidase III (DPP III) family of enzymes and confirmed peptidase activity toward DPP III substrates. In light of these investigations, an extensive computational study was performed in order to improve understanding of the AFO functions. Steered MD simulations revealed long‐range domain motions described as protein opening, characteristic for DPPs III and necessary for substrate binding. Newly identified open and partially open forms of the enzyme closely resemble those of the human DPP III orthologue. Docking of a synthetic DPP III substrate Arg2‐2‐naphthylamide revealed a binding mode similar to the one found in crystal structures of human DPP III complexes with peptides with the S1 and S2 subsites’ amino acid residues conserved. On the other hand, no energetically favorable AFB1 binding mode was detected, suggesting that aflatoxins are not good substrates of AFO. High plasticity of the zinc ion coordination sphere within the active site, consistent with that of up to date studied DPPs III, was observed as well. A detailed electrostatic analysis of the active site revealed a predominance of negatively charged regions, unsuitable for the binding of the neutral AFB1. The present study is in line with the most recent experimental study on this enzyme, both suggesting that AFO is a typical member of the DPP III family.
Nanotube‐mediated cross‐feeding couples the metabolism of interacting bacterial cells

Bacteria frequently engage in cross-feeding interactions that involve an exchange of metabolites with other micro- or macroorganisms. The often obligate nature of these associations, however, hampers manipulative experiments, thus limiting our mechanistic understanding of the ecophysiological consequences that result for the organisms involved. Here we address this issue by taking advantage of a well-characterized experimental model system, in which auxotrophic genotypes of E. coli derive essential amino acids from prototrophic donor cells using intercellular nanotubes. Surprisingly, donor-recipient cocultures revealed that the mere presence of auxotrophic genotypes was sufficient to increase amino acid production levels of several prototrophic donor genotypes. Our work is consistent with a scenario, in which interconnected auxotrophs withdraw amino acids from the cytoplasm of donor cells, which delays feedback inhibition of the corresponding amino acid biosynthetic pathway and, in this way, increases amino acid production levels. Our findings indicate that in newly established mutualistic associations, an intercellular regulation of exchanged metabolites can simply emerge from the architecture of the underlying biosynthetic pathways, rather than requiring the evolution of new regulatory mechanisms.
Safety of recombinant coagulation factors in treating hemophilia

ABSTRACT Introduction: During the last decade, new FVIII/IX concentrates have been developed for the treatment of patients affected by hemophilia A/B. Significant progress has been achieved regarding their half-life, but the old issue of immunogenicity and new concerns about safety need to be addressed. Areas covered: After the implementation of virucidal methods, both plasma-derived and recombinant clotting factor concentrates achieved a very safe profile. The development of anti-FVIII antibodies is the major adverse event of replacement therapy with both FVIII concentrates. Furthermore, the new extended half-life concentrates, protein fused or pegylated, raised some concerns about their side effects. Expert Opinion: The treatment of hemophilia A with inhibitors by induction of immunotolerance and using by-passing concentrates, improved the quality of life of patients but did not allow them to have a life expectancy like that of patients without inhibitors. The new humanized monoclonal antibody (MAb) ACE910, mimicking FVIII function, seems to be able to reduce the bleedings of hemophilia A patients with inhibitors. The post-marketing surveillance will clarify if the adverse events observed during the phase III clinical trials and compassionate use were due to the association with a Prothrombin activated complex concentrate or to the prothrombotic effect of the drug itself.