Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonrandom Distribution of Azole Resistance across the Global Population of Aspergillus fumigatus

Azole drug resistance in the human-pathogenic fungus Aspergillus fumigatus continues to emerge, potentially leading to untreatable aspergillosis in immunosuppressed hosts. Two dominant, environmentally associated resistance mechanisms, which are thought to have evolved through selection by the agricultural application of azole fungicides, are now distributed globally. Understanding the effect that azole resistance is having on the genetic diversity and global population of A. fumigatus will help mitigate drug-resistant aspergillosis and maintain the azole class of fungicides for future use in both medicine and crop protection. ABSTRACT The emergence of azole resistance in the pathogenic fungus Aspergillus fumigatus has continued to increase, with the dominant resistance mechanisms, consisting of a 34-nucleotide tandem repeat (TR34)/L98H and TR46/Y121F/T289A, now showing a structured global distribution. Using hierarchical clustering and multivariate analysis of 4,049 A. fumigatus isolates collected worldwide and genotyped at nine microsatellite loci using analysis of short tandem repeats of A. fumigatus (STRAf), we show that A. fumigatus can be subdivided into two broad clades and that cyp51A alleles TR34/L98H and TR46/Y121F/T289A are unevenly distributed across these two populations. Diversity indices show that azole-resistant isolates are genetically depauperate compared to their wild-type counterparts, compatible with selective sweeps accompanying the selection of beneficial mutations. Strikingly, we found that azole-resistant clones with identical microsatellite profiles were globally distributed and sourced from both clinical and environmental locations, confirming that azole resistance is an international public health concern. Our work provides a framework for the analysis of A. fumigatus isolates based on their microsatellite profile, which we have incorporated into a freely available, user-friendly R Shiny application (AfumID) that provides clinicians and researchers with a method for the fast, automated characterization of A. fumigatus genetic relatedness. Our study highlights the effect that azole drug resistance is having on the genetic diversity of A. fumigatus and emphasizes its global importance upon this medically important pathogenic fungus. IMPORTANCE Azole drug resistance in the human-pathogenic fungus Aspergillus fumigatus continues to emerge, potentially leading to untreatable aspergillosis in immunosuppressed hosts. Two dominant, environmentally associated resistance mechanisms, which are thought to have evolved through selection by the agricultural application of azole fungicides, are now distributed globally. Understanding the effect that azole resistance is having on the genetic diversity and global population of A. fumigatus will help mitigate drug-resistant aspergillosis and maintain the azole class of fungicides for future use in both medicine and crop protection.
Association between feed sorting and the prevalence of metabolic disorders in Hungarian large-scale dairy herds.

This research communication describes the possible association between feed sorting and the risk of metabolic disorders in dairy cows. Feed sorting, that is selecting smaller size TMR particles over longer length fibers, can lead to imbalanced energy input. In addition, sorting can lead to lower nutritive value of leftover TMR. To detect a possible relationship between TMR sorting and the occurrence of metabolic disorders in large-scale herds, TMR separation and metabolic profile tests were performed in 22 Hungarian dairies. Feed sorting was defined as >5% alteration in the mass proportion of any of the TMR fractions between the time of feed distribution and 5-6 h later. The prevalence of ketosis and subclinical acidosis differed between feed sorting and non-sorting groups. Inhomogeneous TMR seems to be a predisposing factor for imbalanced energy status. TMR homogeneity measurements should be routinely included in herd health monitoring.
Serratus anterior plane block for upper abdominal incisions

Regional anaesthetic techniques for patients undergoing laparotomy have been shown to provide optimal postoperative analgesia and allow early mobilisation, and thus, enhance recovery. The serratus anterior plane block, first documented in 2013, has been suggested as a potential alternative to thoracic paravertebral and central neuraxial blockade for chest wall and upper abdominal incisions as it can provide analgesia from T2 to T9. Although there are published cases of this block being used for chest wall analgesia, there are currently no published cases of this block being used for abdominal incisions. We report our experience with two patients, using ultrasound-guided serratus anterior plane blockade with catheter insertion following laparotomy.
The evolution of family‐centered care: From supporting parent‐delivered interventions to a model of family integrated care

There is increasing recognition that parents play a critical role in promoting the health outcomes of low birthweight and preterm infants. Despite a large body of literature on interventions and models to support family engagement in infant care, parent involvement in the delivery of care for such infants is still restricted in many neonatal intensive care units (NICUs). In this article, we propose a taxonomy for classifying parent‐focused NICU interventions and parent‐partnered care models to aid researchers, clinical teams, and health systems to evaluate existing and future approaches to care. The proposed framework has three levels: interventions to support parents, parent‐delivered interventions, and multidimensional models of NICU care that explicitly incorporate parents and partners in the care of their preterm or low birthweight infant. We briefly review the available evidence for interventions at each level and highlight the strong level of research evidence to support the parent‐delivered intervention of skin‐to‐skin contact (also known as the Kangaroo Care position) and for the Kangaroo mother care and family integrated care models of NICU care. We suggest directions for future research and model implementation to improve and scale‐up parent partnership in the care of NICU infants.
Polarimetric Properties of Diffuse Scattering From Building Walls: Experimental Parameterization of a Ray-Tracing Model

Dense multipath components may represent an important part of wireless transmission channels, yet little is known about their physical properties. For this reason, we parameterize an ad hoc diffuse scattering model, which can be easily included in ray-tracing tools. The work, focusing on the polarimetric properties of diffuse contributions scattered off building walls, relies on experimental data. By means of a joint post-processing of the data in conjunction with ray-tracing simulations, characteristic parameters of diffuse scattering are extracted. The analysis reveals that diffuse scattering represents an crucial part of the received power. Regarding depolarization caused by diffuse scattering, our work highlights that depolarization appears to be small for homogeneous brick walls, but is far from negligible for more complex wall structures.
Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer

Pancreatic cancer (PC) is insidious with a high mortality rate due to the lack of symptomology prior to diagnosis. Mitochondrial involvement in PC development is becoming accepted, and exposure to cadmium (Cd) is suspected of being a risk factor for the development of PC; however, the mechanisms involved remain unclear. In this study, we examined the role of Cd as a mitochondrial toxicant and whether alterations in mitochondrial function may be an underlying cause for the development of PC. In this study, cadmium chloride (CdCl2)-mediated toxicity in hTERT-HPNE and AsPC-1 pancreatic cell lines was determined by MTT assay. We also investigated the release of LDH and the generation of free radicals. Mitochondrial toxicity assays were performed in media containing glucose (25 mM) or galactose (10 mM) and following exposure to CdCl2 (0-100 μM) followed by MTT assay. For the confirmation of mitochondrial toxicity, we measured the release of ATP following exposure to CdCl2. Initial experiments confirmed that exposure to CdCl2 did not reduce the viability of either cell line until a concentration of >10 μM was used. Non-linear analysis of the response curves revealed lethal concentration 50% (LC50) values for CdCl2 in the HPNE cells of 77 μM compared to 42 μM in the AsPC-1 cells (P<0.01). The CdCl2-mediated mitochondrial toxic effects were greater in the HPNE cells, suggesting a heightened sensitivity to the effects of CdCl2, not due to elevated oxidative stress. Increased mitochondrial toxic sensitivity was indicated by a 73.4% reduction in IC50 values in the HPNE cells cultured in galactose compared to culture in glucose media, whereas the AsPC-1 cells exhibited a 58.8% reduction in IC50 values. In addition, the higher concentration of CdCl2 elicited a significant cell-dependent effect on ATP release in both cell lines, suggestive of CdCl2 being a mitochondrial toxicant. Cell survival was unaffected following exposure to low concentrations of CdCl2; however, exposure did alter mitochondrial function (control cells > tumor cells). Therefore, the findings of this study indicate that the mitochondria may be a site of action for cadmium in promoting tumor development.
Approach to infection and disease due to adenoviruses in solid organ transplantation.

PURPOSE OF REVIEW Adenoviruses are an important cause of morbidity and mortality of solid organ transplant patients and remain a clinical challenge with regard to diagnosis and treatment. In this review, we provide an approach to identification and classification of adenovirus infection and disease, highlight risk factors, and outline management options for adenovirus disease in solid organ transplant patients. RECENT FINDINGS Additional clinical data and pathologic findings of adenovirus disease in different organs and transplant recipients are known. Unlike hematopoietic cell transplant recipients, adenovirus blood PCR surveillance and preemptive therapy is not supported in solid organ transplantation. Strategies for management of adenovirus disease continue to evolve with newer antivirals, such as brincidofovir and adjunctive immunotherapies, but more studies are needed to support their use. SUMMARY Distinguishing between adenovirus infection and disease is an important aspect in adenovirus management as treatment is warranted only in symptomatic solid organ transplant patients. Supportive care and decreasing immunosuppression remain the mainstays of management. Cidofovir remains the antiviral of choice for severe or disseminated disease. Given its significant nephrotoxic effect, administration of probenecid and isotonic saline precidofovir and postcidofovir infusion is recommended.
Fractal fluctuations in exploratory movements predict differences in dynamic touch capabilities between children with Attention-Deficit Hyperactivity Disorder and typical development

Children with Attention-Deficit Hyperactivity Disorder (ADHD) struggle to perform a host of daily activities. Many of these involve forceful interaction with objects and thus implicate dynamic touch. Therefore, deficits in dynamic touch could underlie functional difficulties presented by ADHD children. We investigated whether performance on a dynamic touch task (length perception by wielding) differ between children with ADHD and age-matched controls. We further examined whether this difference could be explained by fractal temporal correlations (wielding dynamics). Forty-two children (ADHD: 21; typically developing: 21) wielded unseen wooden rods and reported their perceived length in the form of magnitude productions. The rods varied in the magnitude of the first principal moment of inertia (I1). Three-dimensional displacements of hand and rod positions were submitted to Detrended Fluctuation Analysis to estimate trial-by-trial temporal correlations. Children with ADHD reported shorter length for rods with higher I1 than their typically developing peers, indicative of reduced sensitivity to mechanical information supporting dynamic touch. Importantly, temporal correlations in wielding dynamics moderated children’s usage of I1. This finding points to a role of exploratory movements in perceptual deficits presented by children with ADHD and, thus, should be considered a new potential target for interventions.
Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study.

PURPOSE Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes. PATIENTS AND METHODS Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS). RESULTS High PET score was associated with inferior EFS, before (P < .001) and after adjustment (P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P > .4). CONCLUSION In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.
What Is Meaningful Participation for Older People? An Analysis of Aging Policies.

BACKGROUND AND OBJECTIVES The language used to construct policy problems influences the solutions created. Recent aging policies emphasize participation as essential to aging well, encouraging independence and active involvement in all aspects of life. However, it is less clear whether participation in the creation of policies or in policy goals and aspirations is meaningful. This article addresses the question: "How is meaningful participation reflected and enabled in policy? " RESEARCH DESIGN AND METHODS Eleven global, national, and local policies were purposively selected and analyzed using thematic and discourse analysis. RESULTS Policies framed population aging as a challenge and active aging as a value as or part of the policy-making process, participation is enabled (or not) through the types of participation encouraged by policy makers and the kinds of participation used to engage with older people. DISCUSSION AND IMPLICATIONS Our analysis identifies a strong pattern of discourses regarding individual responsibility to age well; underlying tensions between productive and passive participation; and tensions inherent to the concept of consultation. Implications include the need for those in the consultative phase of policy making to engage with diverse older people and to use participatory methods to explore what meaningful participation means for older people themselves.
Adenomatous Polyposis Coli Gene Mutations in 22 Chinese Pedigrees with Familial Adenomatous Polyposis

Background Familial adenomatous polyposis (FAP), which has a very high tendency of progression to colorectal cancer, is mainly caused by mutations of the adenomatous polyposis coli (APC) gene. This study systematically screened the APC mutations and observed the correlation of APC mutations with clinical manifestations of FAP. Material/Methods Eighty subjects (probands and their family members of 22 FAP pedigrees) were enrolled, underwent abdominal ultrasound, computed tomography, and colonoscopic examinations, and were assessed for APC mutations between January 2010 and June 2015 at Tianjin Union Medical Center. Peripheral blood was collected from subjects, and DNA was extracted and screened for APC mutations using multiplex ligation-dependent probe amplification for large-fragment deletions or PCR-denaturing high-performance liquid chromatography with DNA sequencing for micromutations. Results Nineteen of 22 FAP pedigrees were found to have mutations of APC, and 17 types APC mutations were identified. All the mutations were heterozygosity with autosomal dominant inheritance. APC mutations included 8 caused by frameshift, 3 by aberrant splicing, 2 by missense mutation, 2 by nonsense mutation, and 2 by large-fragment deletion. Frameshift mutation was the most common type of APC mutation, and Coding DNA Sequence 15 was the most common mutation site. Five novel APC mutations, including 1 with large-fragment deletion, were identified. Conclusions We systematically screened 17 mutations of APC from 22 Chinese pedigrees with FAP. This study will broaden the spectrum of known APC germline mutations and help understand the types and distribution of APC mutations among Chinese patients with FAP.
An algorithm for the constrained two-dimensional rectangular multiple identical large object placement problem

This paper presents an algorithm for the constrained, two-dimensional, rectangular multiple identical large object placement problem, where a set of small rectangular items must be cut from a specified number of identical plates, so as to maximize the value of the cut items. The algorithm generates optimal homogenous T-shape patterns that contain only homogenous strips. A homogenous strip contains items of the same type. A cut divides the plate into two segments. Each segment consists of strips with the same direction. The strips in the first segment are horizontal, and those in the second segment are vertical. The algorithm is based on the bottom-up tree-search approach. Both lower and upper bounds are used to prune the search tree. The computational results indicate that the algorithm is capable of solving problems of small and medium scales.
Antithrombotic effect of epigallocatechin gallate on the patency of arterial microvascular anastomoses

Background Microvascular anastomosis patency is adversely affected by local and systemic factors. Impaired intimal recovery and endothelial mechanisms promoting thrombus formation at the anastomotic site are common etiological factors of reduced anastomosis patency. Epigallocatechin gallate (EGCG) is a catechin derivative belonging to the flavonoid subgroup and is present in green tea (Camellia sinensis). This study investigated the effects of EGCG on the structure of vessel tips used in microvascular anastomoses and evaluated its effects on thrombus formation at an anastomotic site. Methods Thirty-six adult male Wistar albino rats were used in the study. The right femoral artery was cut and reanastomosed. The rats were divided into two groups (18 per group) and were systemically administered either EGCG or saline. Each group were then subdivided into three groups, each with six rats. Axial histological sections were taken from segments 1 cm proximal and 1 cm distal to the microvascular anastomosis site on days 5, 10, and 14. Results Thrombus formation was significantly different between the EGCG and control groups on day 5 (P=0.015) but not on days 10 or 14. The mean luminal diameter was significantly greater in the EGCG group on days 5 (P=0.002), 10 (P=0.026), and 14 (P=0.002). Intimal thickening was significantly higher on days 5 (P=0.041) and 10 (P=0.02). Conclusions EGCG showed vasodilatory effects and led to reduced early thrombus formation after microvascular repair. Similar studies on venous anastomoses and random or axial pedunculated skin flaps would also contribute valuable findings relevant to this topic.
IDEA AND PERSPECT IVE Predictability in community dynamics

Benjamin Blonder,* Derek E. Moulton, Jessica Blois, Brian J. Enquist, Bente J. Graae, Marc Macias-Fauria, Brian McGill, Sandra Nogu e, Alejandro Ordonez, Brody Sandel and Jens-Christian Svenning Abstract The coupling between community composition and climate change spans a gradient from no lags to strong lags. The no-lag hypothesis is the foundation of many ecophysiological models, correlative species distribution modelling and climate reconstruction approaches. Simple lag hypotheses have become prominent in disequilibrium ecology, proposing that communities track climate change following a fixed function or with a time delay. However, more complex dynamics are possible and may lead to memory effects and alternate unstable states. We develop graphical and analytic methods for assessing these scenarios and show that these dynamics can appear in even simple models. The overall implications are that (1) complex community dynamics may be common and (2) detailed knowledge of past climate change and community states will often be necessary yet sometimes insufficient to make predictions of a community’s future state.
Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts.

OBJECTIVE Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having proformation properties. The purpose of this study was to investigate the importance of the ephrin system in OA subchondral bone osteoblasts. METHODS The presence of the EphB4 receptor was determined by immunohistochemistry, and its expression level, modulation upon treatment, and consequences of activation by ephrin B2 were determined by quantitative polymerase chain reaction. The effects of ephrin B2 activation of the EphB4 receptor on bone resorption activity were also determined. EphB4 receptor activation signaling pathways were investigated by specific enzyme-linked immunosorbent assay. RESULTS EphB4 receptors were present in subchondral bone osteoblasts and osteocytes. Compared with normal and H-OA osteoblasts, EphB4 receptor expression levels were significantly increased in L-OA osteoblasts, with no difference between normal and H-OA osteoblasts. EphB4 receptor levels in L-OA osteoblasts were significantly up-regulated by prostaglandin E2 (PGE2) and interleukin-17 (IL-17). Ephrin B2, PGE2, and IL-17 significantly inhibited bone resorption activity in these cells. EphB4 activation by ephrin B2 significantly inhibited the expression of IL-1beta, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-9, MMP-13, and RANKL, but not MMP-2 and osteoprotegerin. EphB4 receptor activation significantly inhibited the phosphatidylinositol 3-kinase/Akt pathway. CONCLUSION This study is the first to provide evidence that EphB4 receptor activation by ephrin B2 in OA subchondral bone could affect abnormal metabolism in this tissue by inhibiting resorption factors and their activities. Ephrin B2 could be targeted as a specific therapeutic approach in the development of a disease-modifying OA drug.