Miracle-dz/UniFAR-FTUs huggingface dataset:
Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats

The anti‐catabolic bisphosphonate alendronate is considered as the first‐line medical treatment in post‐menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague‐Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 μg/mL/d), alendronate (70 μg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 μg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline‐treated OVX group presented an extreme decrease in calcified area in opposition to melatonin‐ or alendronate‐treated groups, while the bones in alendronate + melatonin‐treated group were similar to those of the sham‐operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate‐ or melatonin‐treated groups. Oxidative gastric damage was increased in saline‐ or alendronate‐treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX‐induced gastric injury, which was aggravated by alendronate use.
Fire Blight Management in the Twenty-first Century: Using New Technologies that Enhance Host Resistance in Apple.

Fire blight has been known as a destructive disease of apple and pear for over 200 years (3). The disease is caused by the bacterium Erwinia amylovora, which is capable of infecting blossoms, fruits, vegetative shoots, woody tissues, and rootstock crowns (Fig. 1). There are several distinct phases of the disease including blossom blight, shoot blight, and rootstock blight. The diversity of host tissues susceptible to infection, combined with the limited number of management tools available to control the disease, has made it difficult to stop or slow the progress of fire blight epidemics. Effective management of fire blight requires an integrated approach of several practices that are aimed at (i) reducing the amount of inoculum that is available to initiate new infections, (ii) imposing barriers to successful establishment of the pathogen on the host, and (iii) reducing host susceptibility to infection (1,55). Most fire blight management strategies developed during the twentieth century focused on the reduction of inoculum in the orchard and the use of antimicrobial treatments to prevent infection. Although increasing host resistance has been recognized as an important component of fire blight management, its application has been limited by a lack of resistant cultivars suited to commercial needs and by a lack of management practices that could effectively increase resistance. Recent advances have made it feasible to change this paradigm in the twenty-first century. First, apple rootstock breeding programs have developed size-controlling (often dwarfing) rootstocks that are resistant to fire blight and are currently becoming available for commercial use (43). Second, genetic engineering of commercial apple cultivars for increased fire blight resistance has been demonstrated, and transgenic apple plants are now undergoing field trials (2). Third, chemical treatments that enhance host resistance have been demonstrated to be useful in the control of fire blight (9,33,61). Although these technologies are at the early stages of development and are either not available or not proven in the marketplace, incorporating the use of host resistance into fire blight management strategies has become a realistic goal in the twenty-first century. This article describes recent progress in the development of new fire blight control technologies that enhance host resistance by chemical or genetic means.
A versatile platform strain for high-fidelity multiplex genome editing

Precision genome editing accelerates the discovery of the genetic determinants of phenotype and the engineering of novel behaviors in organisms. Advances in DNA synthesis and recombineering have enabled high-throughput engineering of genetic circuits and biosynthetic pathways via directed mutagenesis of bacterial chromosomes. However, the highest recombination efficiencies have to date been reported in persistent mutator strains, which suffer from reduced genomic fidelity. The absence of inducible transcriptional regulators in these strains also prevents concurrent control of genome engineering tools and engineered functions. Here, we introduce a new recombineering platform strain, BioDesignER, which incorporates (1) a refactored λ-Red recombination system that reduces toxicity and accelerates multi-cycle recombination, (2) genetic modifications that boost recombination efficiency, and (3) four independent inducible regulators to control engineered functions. These modifications resulted in single-cycle recombineering efficiencies of up to 25% with a seven-fold increase in recombineering fidelity compared to the widely used recombineering strain EcNR2. To facilitate genome engineering in BioDesignER, we have curated eight context-neutral genomic loci, termed Safe Sites, for stable gene expression and consistent recombination efficiency. BioDesignER is a platform to develop and optimize engineered cellular functions and can serve as a model to implement comparable recombination and regulatory systems in other bacteria.
First Report of Citrus leprosis virus in Panama.

Citrus is a rapidly expanding fruit crop in Panama with a planted area of approximately 14,000 ha, with the crop destined for both table and juice industries for local and foreign markets. Chiriqui Province in extreme western Panama borders Costa Rica and grows 4,300 ha of citrus that consists primarily of Valencia and navel oranges with the remainder grown throughout other provinces. Some plants in commercial groves in Potrerillos and Boquete in Chiriqui Province were found with leaf (chlorotic spots or rings), stem (necrosis), and fruit (localized ringlike or depressed lesions) symptoms similar to those caused by Citrus leprosis virus (CiLV) (3). In Potrerillos, wood samples about 3 years old were identified in two of the citrus groves, indicating that the infection was established on or before 1996. The mite Brevipalpus phoenicis (Geijskes) (Acari: Tenuipalpidae) was collected in all leprosis-infected or suspected groves in both Potrerillos and Boquete. CiLV is known to be transmitted by B. obovatus Donnadieu and B. phoenicis in Argentina and Brazil, respectively (3). To confirm the presence of this virus, 20 samples (12 from Boquete [B] and 8 from Potrerillos [P]) of leaf and fruit lesions were fixed in a modified Karnovsky solution and sent to Brazil for electron microscopic examination of thin sections. In 8 samples (2 from B and 6 from P) cytopathic effects were found characterized by a dense viroplasm in the cytoplasm and short, bacilliform particles (50 to 60 × 100 to 110 nm) in the lumen of the endoplasmic reticulum, features similar to those reported by Colariccio et al. (1). In 6 samples (5 from B, and 1 from P), the cytopathic effects were similar to those observed in Orchid fleck virus (OFV)-infected cells (2), with an intranuclear, electron lucent viroplasm and short, rodlike particles (40 to 50 nm × 100 nm) either within the nucleus or in the cytoplasm, as also previously reported for a sample of CiLV in Brazil (4). The symptomatology, presence of the mite vector, characteristic cytopathic effects, and presence of virions are considered to be evidence that CiLV is present within a 100 km2 area of Potrerillos and 25 km2 of Boquete in Chiriqui Province. This is the first report of the presence of CiLV in Central America, suggesting that the virus has spread northward from South America. References: (1) A. Colariccio et al. Fitopatol. Bras. 20:208, 1995. (2) Y. Doi et al. AAB/CMI Description of Plant Viruses No. 183, 1977. (3) S. M. Garnsey and C. M. Chagas. 2000. Pages 57-58 in: Compendium of Citrus Diseases, 2nd Ed. L. W. Timmer et al, eds. APS Press, St.Paul, MN. (4) E. W. Kitajima et al. Virology 50:254, 1972.
Transfer Printing and its Applications in Flexible Electronic Devices

Flexible electronic systems have received increasing attention in the past few decades because of their wide-ranging applications that include the flexible display, eyelike digital camera, skin electronics, and intelligent surgical gloves, among many other health monitoring devices. As one of the most widely used technologies to integrate rigid functional devices with elastomeric substrates for the manufacturing of flexible electronic devices, transfer printing technology has been extensively studied. Though primarily relying on reversible interfacial adhesion, a variety of advanced transfer printing methods have been proposed and demonstrated. In this review, we first summarize the characteristics of a few representative methods of transfer printing. Next, we will introduce successful demonstrations of each method in flexible electronic devices. Moreover, the potential challenges and future development opportunities for transfer printing will then be briefly discussed.
Three neglected numbers in the CBC: The RDW, MPV, and NRBC count

The complete blood cell count (CBC) is one of the most frequently ordered laboratory tests, but some values included in the test may be overlooked. This brief review discusses 3 potentially underutilized components of the CBC: the red blood cell distribution width (RDW), the mean platelet volume (MPV), and the nucleated red blood cell (NRBC) count. These results have unique diagnostic applications and prognostic implications that can be incorporated into clinical practice. By understanding all components of the CBC, providers can learn more about the patient’s condition. These values have diagnostic utility and potential prognostic significance.
Factor Structure and Psychometric Properties of the Resilience Scale for Adolescents (READ)

Psychometric evaluations of the Resilience Scale for Adolescents (READ) have yielded inconsistent support for the original five-factor solution, with different modifications being proposed. The aim of the present article was to investigate the psychometric properties and factor structure of the READ using both confirmatory and exploratory methods, and to evaluate how the scale fits within the theoretical framework of resilience. Data stem from the population-based youth@hordaland-study of 9,596 adolescents from 16 to 19 years of age. Using confirmatory factor analysis, the original five-factor model yielded relatively poor fit. A better model fit was identified for a different five-factor structure using exploratory methods including two new personal factors measuring (a) Goal Orientation and (b) Self-Confidence. This division was supported by low secondary loadings and moderate correlations between the factors, and gender differences in the mean scores. Although the READ is a multidimensional measure that includes individual, family, and social factors related to the resilience process, some important aspects of resilience have not been included.
Blood Pressure–Lowering Treatment With Candesartan in Patients With Acute Hemorrhagic Stroke

Background and Purpose— Early and intensive blood pressure–lowering treatment seems to be beneficial in patients with acute hemorrhagic stroke and high blood pressure. We wanted to see if similar benefits can be shown from a later and more gradual blood pressure lowering, using data from the Scandinavian Candesartan Acute Stroke Trial (SCAST). Methods— SCAST was a randomized- and placebo-controlled, double-masked trial of candesartan given for 7 days, in 2029 patients with acute stroke and systolic blood pressure ≥140 mm Hg. We assessed the effects of candesartan in the 274 patients with hemorrhagic stroke, using the trial’s 2 coprimary effect variables: the composite vascular end point of vascular death, stroke or myocardial infarction, and functional outcome at 6 months, according to the modified Rankin Scale. We used Cox proportional hazards models and ordinal regression for analysis and adjusted for key, predefined prognostic variables. Results— There was no association between treatment with candesartan and risk of vascular events (17 of 144 [11.8%] versus 13 of 130 [10.0%]; hazard ratio, 1.36; 95% confidence interval, 0.65–2.83; P=0.41). For functional outcome we found evidence of a negative effect of candesartan (common odds ratio, 1.61; 95% confidence interval, 1.03–2.50; P=0.036). Conclusions— There was no evidence that blood pressure–lowering treatment with candesartan is beneficial during the first week of hemorrhagic stroke. Instead, there were signs that such treatment may be harmful, but this needs to be verified in larger studies. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT00120003.
Selection and Characterization of a Reovirus Mutant with Increased Thermostability

Nonenveloped viruses rely on protein-protein interactions to shield their genomes from the environment. The capsid, or protective shell, must also disassemble during cell entry. In this work, we identified a determinant within mammalian orthoreovirus that regulates heat resistance, disassembly kinetics, and replicative fitness. Together, these findings show capsid function is balanced for optimal replication and for spread to a new host. ABSTRACT The environment represents a significant barrier to infection. Physical stressors (heat) or chemical agents (ethanol) can render virions noninfectious. As such, discrete proteins are necessary to stabilize the dual-layered structure of mammalian orthoreovirus (reovirus). The outer capsid participates in cell entry: (i) σ3 is degraded to generate the infectious subviral particle, and (ii) μ1 facilitates membrane penetration and subsequent core delivery. μ1-σ3 interactions also prevent inactivation; however, this activity is not fully characterized. Using forward and reverse genetic approaches, we identified two mutations (μ1 M258I and σ3 S344P) within heat-resistant strains. σ3 S344P was sufficient to enhance capsid integrity and to reduce protease sensitivity. Moreover, these changes impaired replicative fitness in a reassortant background. This work reveals new details regarding the determinants of reovirus stability. IMPORTANCE Nonenveloped viruses rely on protein-protein interactions to shield their genomes from the environment. The capsid, or protective shell, must also disassemble during cell entry. In this work, we identified a determinant within mammalian orthoreovirus that regulates heat resistance, disassembly kinetics, and replicative fitness. Together, these findings show capsid function is balanced for optimal replication and for spread to a new host.
Endemic Lake Baikal sponges from deep water. 2: Taxonomy and Bathymetric Distribution.

Unique samples of deep-water sponges of Lake Baikal were collected between 120 and 1450 m depth and their taxonomy and bathymetric distribution were studied. Based on morphological studies with scanning electron microscopy (SEM) and molecular analyses (CO1, ITS) we describe a new species, Baikalospongia abyssalis sp. nov. Spicule morphology of this new species is similar to Palaeoephydatia sp. , a species previously known only from fossils in Late Pliocene (3.2-2.8 mya) sediments. Other sponge samples collected were identified as Baikalospongia intermedia intermedia, B. intermedia profundalis, B. bacillifera, B. fungiformis, B. martinsoni and Swartschewskia papyracea, all from the family Lubomirskiidae. Sponge specimens with giant spicules, identified as B. fungiformis, were found at great depths. B.i. intermedia and B. i. profundalis are dominating species at great depth. Light is a limiting factor for distribution of Lubomirskia baicalensis, possibly due to its symbiosis with photosynthetic protists. The current study extends our knowledge on the distribution boundaries of Lubomirskiidae at great depths.
Estimation of Signal-to-Noise Ratios in Realistic Sound Scenarios.

BACKGROUND Both in the design of hearing-device features, such as noise reduction, and in the evaluation measurements of such features, there is a need for more information about the sound scenarios hearing-device users encounter. The limitations of adaptive speech tests as outcome measures in the evaluation of hearing-device features have been discussed. The obvious alternative to adaptive speech testing is to test at a fixed signal-to-noise ratio (SNR). However, the question is which SNRs should be used if the test reflects real-life situations. PURPOSE The purpose of this study was to estimate SNRs in realistic sound environments encountered by hearing aid users. RESEARCH DESIGN Research design was a descriptive study where recorded sound files were statistically analyzed. STUDY SAMPLE A total of 20 experienced, bilaterally fitted hearing aid users, all satisfied with their current hearing aids, made recordings for 3-4 days. The informants were instructed to record different situations in daily life and were told that all situations were of equal importance. The informants ranged in age from 18-81 yr old, and they had various occupations and varying hearing-loss configurations. DATA COLLECTION AND ANALYSIS The total duration of the recorded material for each informant was, on average, 84 min; the number of recordings was, on average, 17 per informant. The sound files were categorized based on the type of background noise and were analyzed with use of a manual noise estimation procedure. Segments of speech with noise present were cut out from the original recordings. Corresponding noise-only segments were also extracted. On the basis of power calculations for these two types of recorded segments, the SNR was estimated. Frequency-specific and overall SNRs, calculated both based on unweighted and A-weighted speech and noise levels, were derived. An estimation uncertainty measure was also developed. RESULTS The range of SNRs found in the material was large. The most striking finding was that there were very few recorded situations where the SNR was negative or even close to 0 dB. For speech-in-babble noise, the average SNR was approximately 5 dB. The estimation uncertainty was generally low but became higher in highly fluctuating noises and at very low SNRs. CONCLUSIONS The estimated SNRs were higher than previously reported. The results can be used in the design and evaluation of hearing-device features.
Charge‐mediated proteasome targeting

A majority of thousands of intracellular mammalian proteins are recognized by proteasome only being conjugated with ubiquitin (Ub), representing a universal degradation signal operated by the ubiquitination system. Ub‐independent proteasome targeting is rationalized by the existence of 2 types of direct proteasome signals (DPSs), specific amino acid sequences or post‐translational modifications, which are recognized by proteasome regulatory subunits. Historically, the first type was shown to exist in ornithine decarboxylase, whereas acetylation of core histones recently was reported as a second type of DPS. Here we declare a third type, representing charge‐mediated DPS. This discovered DPS may be classified as a monopartite composition‐ but not sequence‐dependent element of ∼70 Å in length enriched in basic and flexible amino acids. This type of degradation signal, which may be provided by cationic chemicals, is most efficiently engaged by proteasomes capped with regulator (REG)α or REGγ in an ATP‐independent manner. Taken together, our findings suggest a novel modality of proteasome‐substrate interrelation bypassing ubiquitination. —Kudriaeva, A. , Kuzina, E. S. , Zubenko, O. , Smirnov, I. V. , Belogurov, A. Charge‐mediated proteasome targeting. FASEB J. 33, 6852–6866 (2019). www.fasebj. org
Perceptions of Strategies and Intervention Approaches for HIV Self-Management among Ugandan Adolescents: A Qualitative Study

The heightened vulnerability of adolescents to poor HIV care outcomes underscores the need for interventions that create and promote HIV self-management behavioral skills. Adolescents living with HIV (ALHIV) experience a complex array of physical, emotional, and social challenges that constrain their self-care, but the majority of existing psychosocial programs focus primarily on medication adherence. Understanding adolescents’ self-care needs, challenges, and preferences is necessary for developing effective culturally relevant interventions. The involvement of caregivers and stakeholders is also critical to realizing positive self-care outcomes. This article presents the findings from focus group discussions with ALHIV, caregivers, and healthcare providers on self-care. The data were collected as part of formative research in the development of a self-management intervention for Ugandan ALHIV. Participants’ discussions on self-care strategies and intervention approaches provide valuable insights to guide the development of interventions to promote positive HIV care outcomes among Ugandan ALHIV.
Rules of anti-infection therapy for sepsis and septic shock

Abstract Objective: Sepsis is a deadly infection that causes injury to tissues and organs. Infection and anti-infective treatment are the eternal themes of sepsis. The successful control of infection is a key factor of resuscitation for sepsis and septic shock. This review examines evidence for the treatment of sepsis. This evidence is combined with clinical experiments to reveal the rules and a standard flowchart of anti-infection therapy for sepsis. Data Sources: We retrieved information from the PubMed database up to October 2018 using various search terms and their combinations, including sepsis, septic shock, infection, antibiotics, and anti-infection. Study Selection: We included data from peer-reviewed journals printed in English on the relationships between infections and antibiotics. Results: By combining the literature review and clinical experience, we propose a 6Rs rule for sepsis and septic shock management: right patients, right time, right target, right antibiotics, right dose, and right source control. This rule encompasses rational decisions regarding the timing of treatment, the identification of the correct pathogen, the selection of appropriate antibiotics, the formulation of a scientifically based antibiotic dosage regimen, and the adequate control of infectious foci. Conclusions: This review highlights how to recognize and treat sepsis and septic shock and provides rules and a standard flowchart for anti-infection therapy for sepsis and septic shock for use in the clinical setting.