Miracle-dz/UniFAR-FTUs huggingface dataset:
Aspergillus fumigatus and pan-azole resistance: who should be concerned?

PURPOSE OF REVIEW Although clinical outcomes in the treatment of aspergillosis have markedly improved with the availability of newer triazoles, the development of resistance to these antifungals, especially in Aspergillus fumigatus, is a growing concern. The purpose of this review is to provide an update on azole resistance mechanisms and their epidemiology in A. fumigatus, the clinical implications of azole resistance, and to discuss future treatment options against azole-resistant aspergillosis. RECENT FINDINGS Resistance may develop through either patient or environmental azole exposure. Environmental exposure is the most prevalent means of resistance development, and these isolates can cause disease in various at-risk groups, which now include those with influenza, and potentially COVID-19. Although current treatment options are limited, newer therapies are in clinical development. These include agents with novel mechanisms of action which have in vitro and in vivo activity against azole-resistant A. fumigatus. SUMMARY Azole-resistant A. fumigatus is an emerging threat that hampers our ability to successfully treat patients with aspergillosis. Certain geographic regions and patient populations appear to be at increased risk for this pathogen. As new patient groups are increasingly recognized to be at increased risk for invasive aspergillosis, studies to define the epidemiology and management of azole-resistant A. fumigatus are critically needed. While treatment options are currently limited, new agents under clinical development may offer hope.
Nifurtimox response of Trypanosoma cruzi isolates from an outbreak of Chagas disease in Caracas, Venezuela

Background & objectives: In Venezuela, Chagas disease (ChD) is considered a serious health problem, with about 6 million people at risk; and acute outbreaks due to oral transmission of Chagas Disease (OChD) are becoming increasingly important. In 2007 there was a major outbreak of OChD and although patients from this episode were treated with nifurtimox (Lampit®—Bayer), about 70% therapeutic failure was registered. These results led us to examine whether parasite’s drug susceptibility was related to this therapeutic failure. Methods: The Trypanosoma cruzi parasites were isolated by haemoculture of the peripheral blood drawn from the pre- and post-nifurtimox treated patients infected in the 2007 OChD outbreak at Caracas, Venezuela. The in vitro assays for drug testing were performed by the MTT methodology followed by calculation of inhibitory concentration-50 (IC50) values. Results: Parasite isolates obtained from the infected patients prior and after nifurtimox treatment when subjected to variable concentrations of the drug showed great heterogeneity in susceptibility with IC50 values ranging from 4.07 ± 1.82 to 94.92 ± 7.24 μM. Interpretation & conclusion: The high heterogeneity in nifurtimox IC50 values in the isolates and clones from the OChD patients, suggests that the therapeutic failure to nifurtimox could be due in part to a phenotypic variability that existed in the wild parasite population at the original source of contamination. Though, further pharmacological studies are needed to confirm the existence of natural nifurtimox resistance in the parasite.
Experience of an 8-Week Online Mindfulness Intervention for Nursing Students: Qualitative Findings.

BACKGROUND Nurses returning to school often have stressors of work, family, and other obligations. Strategies are needed to mitigate the additional stress and promote academic success. Mindfulness is one proposed strategy. PURPOSE The purpose was to explore the experience of students participating in an 8-week mindfulness intervention. METHODS A mixed-methods descriptive study used an emailed survey link with 13 open-ended questions at intervention completion. Interpretive description guided the qualitative analysis. Participant retention, reported practice frequency, and written feedback were analyzed for feasibility and acceptability. RESULTS Twenty-six participants completed the survey. Time commitment, increased awareness, focus and concentration, and enhanced coping were identified themes. Findings supported the impact of mindfulness on student stress, anxiety and cognition, as well as acceptability and feasibility. CONCLUSIONS An online mindfulness program appeared effective, feasible, and acceptable. Qualitative findings informed the quantitative outcomes. Nursing faculty can impact student stress and academic success through mindfulness with their teaching.
Molecular surveillance of methicillin-susceptible Staphylococcus aureus (MSSA) isolated over a one-year period from a Malaysian Teaching Hospital.

Introduction We report the results of a molecular surveillance study carried out on methicillin-susceptible Staphylococcus aureus (MSSA) isolated in a one-year duration from Hospital Canselor Tuanku Muhriz (HCTM), a tertiary hospital located in Kuala Lumpur, Malaysia. Methods The first strain isolated from each MSSA infection in HCTM during the year 2009 was included into the study. Antimicrobial susceptibility testing and agr group typing were carried out for all strains; virulence gene (cna, seh, TSST-1 and PVL) typing results of the strains were obtained from a previous study. Pulsed-field gel electrophoresis (PFGE) was done on selected strains from the orthopedic ward. Relationship(s) between different typing methods used in the study was investigated, where a p value of <0.05 indicated significant association between typing methods. Results A total of 880 MSSA strains were included into the study. The strains were generally susceptible to most antibiotics, with most of them carrying cna and agr-I (51.6%, n=454; 39.8%, n=350, respectively). A total of 17 PFGE pulsotypes were identified using an 80% similarity cut-off value, where the main pulsotype (pulsotype E) consisted of 24 isolates (23.5%). agr-III strains were found to be usually positive for both cna and seh (p<0.05). In addition, some PFGE pulsotypes were also characteristic of certain virulence genes or agr groups. Conclusions We did not identify a dominant MSSA clone circulating in HCTM in 2009. Nevertheless, results from this molecular surveillance will provide good baseline data for the hospital's second S. aureus surveillance planned for the year 2020.
The reasons for Red Data Books

The late Sir Peter Scott, a former President of Fauna and Flora International, proposed the idea of Red Data Books as conservation tools more than 30 years ago. Today, the international Red Data Book programme appears to be effectively at an end, with priority being given to Action Plans and Conservation Assessment Management Plans for groups oftaxa. These, however, cannot entirely replace Red Data Books, and the author of this paper argues that Red Data Books have many vital roles to play in species conservation and makes a plea for their renascence.
A unique bacterial tactic to circumvent the cell death crosstalk induced by blockade of caspase‐8

Upon invasive bacterial infection of colonic epithelium, host cells induce several types of cell death to eliminate pathogens. For instance, necroptosis is a RIPK‐dependent lytic cell death that serves as a backup system to fully eliminate intracellular pathogens when apoptosis is inhibited; this phenomenon has been termed “cell death crosstalk”. To maintain their replicative niche and multiply within cells, some enteric pathogens prevent epithelial cell death by delivering effectors via the type III secretion system. In this study, we found that Shigella hijacks host cell death crosstalk via a dual mechanism: inhibition of apoptosis by the OspC1 effector and inhibition of necroptosis by the OspD3 effector. Upon infection by Shigella, host cells recognize blockade of caspase‐8 apoptosis signaling by OspC1 effector as a key danger signal and trigger necroptosis as a backup form of host defense. To counteract this backup defense, Shigella delivers the OspD3 effector, a protease, to degrade RIPK1 and RIPK3, preventing necroptosis. We believe that blockade of host cell death crosstalk by Shigella is a unique intracellular survival tactic for prolonging the bacterium's replicative niche.
Combining phenome-driven drug-target interaction prediction with patients’ electronic health records-based clinical corroboration toward drug discovery

Abstract Motivation Predicting drug–target interactions (DTIs) using human phenotypic data have the potential in eliminating the translational gap between animal experiments and clinical outcomes in humans. One challenge in human phenome-driven DTI predictions is integrating and modeling diverse drug and disease phenotypic relationships. Leveraging large amounts of clinical observed phenotypes of drugs and diseases and electronic health records (EHRs) of 72 million patients, we developed a novel integrated computational drug discovery approach by seamlessly combining DTI prediction and clinical corroboration. Results We developed a network-based DTI prediction system (TargetPredict) by modeling 855 904 phenotypic and genetic relationships among 1430 drugs, 4251 side effects, 1059 diseases and 17 860 genes. We systematically evaluated TargetPredict in de novo cross-validation and compared it to a state-of-the-art phenome-driven DTI prediction approach. We applied TargetPredict in identifying novel repositioned candidate drugs for Alzheimer’s disease (AD), a disease affecting over 5.8 million people in the United States. We evaluated the clinical efficiency of top repositioned drug candidates using EHRs of over 72 million patients. The area under the receiver operating characteristic (ROC) curve was 0.97 in the de novo cross-validation when evaluated using 910 drugs. TargetPredict outperformed a state-of-the-art phenome-driven DTI prediction system as measured by precision–recall curves [measured by average precision (MAP): 0.28 versus 0.23, P-value < 0.0001]. The EHR-based case–control studies identified that the prescriptions top-ranked repositioned drugs are significantly associated with lower odds of AD diagnosis. For example, we showed that the prescription of liraglutide, a type 2 diabetes drug, is significantly associated with decreased risk of AD diagnosis [adjusted odds ratios (AORs): 0.76; 95% confidence intervals (CI) (0.70, 0.82), P-value < 0.0001]. In summary, our integrated approach that seamlessly combines computational DTI prediction and large-scale patients’ EHRs-based clinical corroboration has high potential in rapidly identifying novel drug targets and drug candidates for complex diseases. Availability and implementation nlp.case. edu/public/data/TargetPredict.
Light-limited growth and competition for light in well-mixed aquatic environments : An elementary model

Light is never distributed homogeneously since it forms a gradient over biomass. As a consequence, the common theories on nutrient competition are not applicable to competition for light. In this paper, we investigate a model for light-limited growth and competition among phytoplankton species in a mixed water column. The model is based on standard assumptions such as Lambert-Beer's law of light absorption, a Monod equation for carbon uptake, and constant specific carbon losses. By introducing the concept of quantum return, we show that the dynamics of growth and competition can be quantified not only in terms of depth but also directly in terms of light availability. We argue that the crucial measure for phytoplankton growth is not a ''critical depth'' but a ''critical light intensity,'' I-out*. For each species, I-out* corresponds to the equilibrium light intensity at the bottom of a water column when the species is grown in monoculture. I-out* plays a role similar to the ''critical nutrient concentration'' R* used in models of nutrient-limited growth. For a constant light supply, the species with the lowest I-out* will competitively exclude all other species. There are, however, some important differences between R* and I-out*. Whereas R* reflects both the local and the total balance between nutrient uptake and nutrient losses, I-out* only reflects the total carbon balance. Moreover, I-out* decreases with increasing light supply, whereas R* is independent of the nutrient supply. As a consequence, (1) the outcome of competition for light may depend on the light supply, (2) the compensation point is not a good predictor for the outcome of competition, (3) the resource ratio hypothesis does not apply when species compete for both nutrients and light. The outcome of competition for nutrients and light may depend on the nutrient and light supply, on the mixing depth, and on the background turbidity due to inanimate substances.
High-frequency plantlet regeneration by somatic embryogenesis from mature zygotic embryos of onion

Somatic embryogenesis is a promising approach for plantlet regeneration. In order to establish a high-frequency plantlet regeneration system of onion in vitro, we used mature zygotic embryos as experimental material to improve the culture protocol. The results showed the highest induction rate of embryogenic callus (91%) was found when the NH4+/NO3– ratio in Murashige and Skoog (MS) medium was adjusted to 30/30 mM/mM. Well-proliferated embryogenic calli were observed in a 3 L airlift balloon-type bioreactor. During bioreactor culture, the continuous immersion culture was better. Inoculation density of 5 g/L and 0.1 vvm (air volume/culture medium volume per min) air volume were optimal for embryogenic callus proliferation. In addition, to obtain mature somatic embryos, the effects of sucrose and thiamine (VB1) were examined. Results showed that 20 g/L sucrose favoured somatic embryo maturation. When the VB1 concentration in normal MS medium (0.1 mg/L) was increased to 10 mg/L, the rate of somatic embryo germination reached 93.3%. When the mature somatic embryos were inoculated in MS medium without plant growth regulators, whole plantlets regenerated after 15 d of culture. During plantlet acclimatisation, the maximum survival rate (93.8%) was found in the substrate of 1/2 vermiculite and 1/2 perlite.
The entorhinal cortex of the monkey: VI. Organization of projections from the hippocampus, subiculum, presubiculum, and parasubiculum

The organization of projections from the macaque monkey hippocampus, subiculum, presubiculum, and parasubiculum to the entorhinal cortex was analyzed using anterograde and retrograde tracing techniques. Projections exclusively originate in the CA1 field of the hippocampus and in the subiculum, presubiculum, and parasubiculum. The CA1 and subicular projections terminate most densely in Layers V and VI of the entorhinal cortex, with sparser innervation of the deep portion of Layers III and II. Entorhinal projections from CA1 and the subiculum are topographically organized such that a rostrocaudal axis of origin is related to a medial‐to‐lateral axis of termination. A proximodistal axis of origin in CA1 and distoproximal axis in subiculum are related to a rostrocaudal axis of termination in the entorhinal cortex. The presubiculum sends a dense, bilateral projection to caudal parts of the entorhinal cortex. This projection terminates most densely in Layer III with sparser termination in Layers I, II, and V. The same parts of entorhinal cortex receive a dense projection from the parasubiculum. This projection terminates in Layers III and II. Both presubicular and parasubicular projections demonstrate the same longitudinal topographic organization as the projections from CA1 and the subiculum. These studies demonstrate that: (a) hippocampal and subicular inputs to the entorhinal cortex in the monkey are organized similar to those described in nonprimate species; (b) the topographic organization of the projections from the hippocampus and subicular areas matches that of the reciprocal projections from the entorhinal cortex to the hippocampus and the subicular areas.
Development of new predictive equations for basal metabolic rate in Iranian healthy adults: negligible effect of sex.

Some studies have reported inaccuracy of predicting basal metabolic rate (BMR) by using common equations for Asian people. Thus, this study was undertaken to develop new predictive equations for the Iranian community and also to compare their accuracy with the commonly used formulas. Anthropometric measures and thyroid function were evaluated for 267 healthy subjects (18-60 y). Indirect calorimetry (InCal) was performed only for those participants with normal thyroid function tests (n = 252). Comparison of predicted RMR (both kcal/d and kcal.kg.wt-1.d-1) using current predictive formulas and measured RMR revealed that Harris-Benedict and FAO/WHO/UNU significantly over-estimated and Mifflin-St. Jeor significantly under-estimated RMR as compared to InCal measurements. In stepwise regression analysis for developing new equations, the highest r2 (=0.89) was from a model comprising sex, height and weight. However, further analyses revealed that unlike the subjects under 30 y, the association between age and the measured RMR in subjects 30 y and plus was negative (r = -0.241, p = 0.001). As a result, two separate equations were developed for these two age groups. Over 80 percent of variations were covered by the new equations. In conclusion, there were statistical significant under- and over-estimation of RMR using common predictive equations in our subjects. Using the new equations, the accuracy of the calculated RMR increased remarkably.
Monitoramento da variabilidade genética de pacu, Piaractus mesopotamicus, do programa de aumento de estoque do rio Paranapanema

Avaliou-se a variabilidade genetica dos estoques de reprodutores e dos peixes jovens de Piaractus mesopotamicus de tres pisciculturas do estado do Parana, utilizadas no programa de aumento de estoque de peixes no rio Paranapanema. Foi utilizado o marcador RAPD para avaliar as amostras do estoque de reprodutores e dos peixes jovens das pisciculturas de Palotina, Cambara e Andira. A porcentagem de fragmentos polimorficos e o indice de diversidade genetica de Shannon dos estoques de reprodutores variaram de 75,0% a 71,4% e de 0,434 a 0,376, respectivamente. Os peixes jovens das pisciculturas apresentaram valores mais elevados para ambos os parâmetros, com excecao da piscicultura de Palotina, na qual o indice de diversidade genetica de Shannon foi semelhante. Os estoques de reprodutores apresentaram alta variabilidade genetica, e esta foi mantida nos peixes jovens.
Assessment of energy expenditure: are calories measured differently for different diets?

Purpose of review The prevalence and burden of obesity has reached alarming levels. The assessment of human energy expenditure enables the identification of obesity-prone and obesity-resistant individuals and helps to explain the short and long-term success of weight loss treatments. In this review, we describe the state-of-the-art methods used in the assessment of human energy expenditure and the impact of dietary intake on the interpretation of the data. Recent findings The reference techniques to assess energy expenditure in humans have not significantly changed during the last century. Today, indirect calorimetry, either using a metabolic chamber or a metabolic cart, is the favored method to assess human energy expenditure and is the only method enabling the assessment of macronutrient oxidation. The doubly labeled water method however provides accurate assessment of human energy expenditure under free living conditions. Summary Although energy expenditure and macronutrient oxidation can be assessed by simple calculations from oxygen consumption and carbon dioxide production, these calculations can provide erroneous results or require corrections and/or more complex interpretation when several biochemical pathways are simultaneously engaged. Such physiological mechanisms are often elicited by dietary interventions including, among other, gluconeogenesis, lipogenesis, ketogenesis, alcohol oxidation and under or overfeeding.
Kalimantanorchis: A New Genus of Mycotrophic Orchid from West Kalimantan, Borneo

Abstract A new genus and species of mycotrophic orchid (Orchidaceae), Kalimantanorchis nagamasui Tsukaya, M. Nakajima et H. Okada, from Betung Kerihun National Park, West Kalimantan, Borneo, Indonesia, is described and illustrated. Kalimantanorchis resembles the genus Tropidia Lindl. in flower and stem morphology, namely, mycotrophic habit, branching stem, nonresupinate flowers with a saccate cymbiform lip bearing two longitudinal ridges along the margins, broadly triangular rostellum, acute, triangular anther cap, and winged or three-lobed column. It differs, however, in having a tuberous root system, pure ivory-white flower coloration and four pollinia. BLAST analyses based on DNA sequences of the chloroplast matK pseudogene and ITS of the nuclear ribosomal DNA also suggest that the closest genus is Tropidia Lindl. , but the similarity is low and a molecular phylogenetic analysis did not support it to be a member of Tropidia, confirming the idea that this is an undescribed genus.
Strategic white matter injury associated with long‐term information processing speed deficits in mild traumatic brain injury

Deficits in information processing speed (IPS) are among the earliest and most prominent cognitive manifestations in mild traumatic brain injury (mTBI). We investigated the impact of white matter fiber location on IPS outcome in an individual basis assessment. A total of 112 acute mild TBI with all CT negative underwent brain DTI and blood sampling for inflammation cytokines within 7 days postinjury and 72 age‐ and sex matched healthy controls with same assessments were enrolled. IPS outcome was assessed by the trail making test at 6–12 month postinjury in mild TBI. Fractional anisotropy (FA) features were extracted using a novel lesion‐load analytical strategy to capture spatially heterogeneous white matter injuries and minimize implicit assumptions of uniform injury across diverse clinical presentations. Acute mild TBI exhibited a general pattern of increased and decreased FA in specific white matter tracts. The power of acute FA measures to identify patients developing IPS deficits with 92% accuracy and further improved to 96% accuracy by adding inflammation cytokines. The classifiers predicted individual's IPS and working memory ratings (r = .74 and .80, respectively, p < .001). The thalamo‐cortical circuits and commissural tracts projecting or connecting frontal regions became important predictors. This prognostic model was also verified by an independent replicate sample. Our findings highlighted damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal‐subcortical neuronal circuits as a predictor for processing speed performance in mild TBI.