Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro and In Vivo Effect of the Imidazole Luliconazole against Lomentospora prolificans and Scedosporium spp.

Lomentospora prolificans and S. apiospermum/P. boydii are opportunistic, multidrug-resistant pathogens causing invasive infections in immunosuppressed patients and sometimes in healthy persons. Lomentospora prolificans is panresistant against the currently available antifungals, and both species are associated with high mortality rates. Thus, the discovery of novel antifungal drugs exhibiting an effect against these resistant fungi is crucial. ABSTRACT Infections with Scedosporium spp. and Lomentospora prolificans have become a serious threat in clinical settings. The high mortality rates associated with these infections can be correlated with their multidrug resistance. The development of alternative treatment strategies has become crucial. Here, we investigate the in vitro and in vivo activity of luliconazole (LLCZ) against Scedosporium apiospermum (including its teleomorph Pseudallescheria boydii) and Lomentospora prolificans. The LLCZ MICs were determined for a total of 37 isolates (31 L. prolificans isolates, 6 Scedosporium apiospermum/P. boydii strains) according to EUCAST. Furthermore, the LLCZ antifungal activity was tested in vitro, using an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] growth kinetics assay and biofilm assays (crystal violet and XTT assay). In addition, a Galleria mellonella infection model was used for in vivo treatment assays. The MIC90 of LLCZ was determined to be 0.25 mg/L for all tested pathogens. Growth was inhibited within 6 to 48 h of the start of incubation. LLCZ inhibited biofilm formation in both preadhesion stages and late-stage adhesion. In vivo, a single dose of LLCZ increased the survival rate of the larvae by 40% and 20% for L. prolificans and Scedosporium spp. , respectively. This is the first study demonstrating LLCZ activity against Lomentospora prolificans in vitro and in vivo and the first study showing the antibiofilm effect of LLCZ in Scedosporium spp. IMPORTANCE Lomentospora prolificans and S. apiospermum/P. boydii are opportunistic, multidrug-resistant pathogens causing invasive infections in immunosuppressed patients and sometimes in healthy persons. Lomentospora prolificans is panresistant against the currently available antifungals, and both species are associated with high mortality rates. Thus, the discovery of novel antifungal drugs exhibiting an effect against these resistant fungi is crucial. Our study shows the effect of luliconazole (LLCZ) against L. prolificans and Scedosporium spp. in vitro, as well as in an in vivo infection model. These data reveal the previously unknown inhibitory effect of LLCZ against L. prolificans and its antibiofilm effect in Scedosporium spp. It represents an extension of the literature regarding azole-resistant fungi and could potentially lead to the development of future treatment strategies against these opportunistic fungal pathogens.
Host Lipid Transport Protein ORP1 Is Necessary for Coxiella burnetii Growth and Vacuole Expansion in Macrophages

Coxiella burnetii is an emerging zoonotic pathogen and bioterrorism threat. No licensed vaccine exists in the United States, and the chronic form of the disease is difficult to treat and potentially lethal. ABSTRACT Coxiella burnetii is an intracellular bacterium that causes the human disease Q fever. C. burnetii forms a large, acidic Coxiella-containing vacuole (CCV) and uses a type 4B secretion system to secrete effector proteins into the host cell cytoplasm. While the CCV membrane is rich in sterols, cholesterol accumulation in the CCV is bacteriolytic, suggesting that C. burnetii regulation of lipid transport and metabolism is critical for successful infection. The mammalian lipid transport protein ORP1L (oxysterol binding protein-like protein 1 Long) localizes to the CCV membrane and mediates CCV-endoplasmic reticulum (ER) membrane contact sites. ORP1L functions in lipid sensing and transport, including cholesterol efflux from late endosomes and lysosomes (LELs), and the ER. Its sister isoform, ORP1S (oxysterol binding protein-like protein 1 Short) also binds cholesterol but has cytoplasmic and nuclear localization. In ORP1-null cells, we found that CCVs were smaller than in wild-type cells, highlighting the importance of ORP1 in CCV development. This effect was consistent between HeLa cells and murine alveolar macrophages (MH-S cells). CCVs in ORP1-null cells had higher cholesterol content than CCVs in wild-type cells at 4 days of infection, suggesting ORP1 functions in cholesterol efflux from the CCV. While the absence of ORP1 led to a C. burnetii growth defect in MH-S cells, there was no growth defect in HeLa cells. Together, our data demonstrated that C. burnetii uses the host sterol transport protein ORP1 to promote CCV development, potentially by using ORP1 to facilitate cholesterol efflux from the CCV to diminish the bacteriolytic effects of cholesterol. IMPORTANCE Coxiella burnetii is an emerging zoonotic pathogen and bioterrorism threat. No licensed vaccine exists in the United States, and the chronic form of the disease is difficult to treat and potentially lethal. Postinfectious sequelae of C. burnetii infection, including debilitating fatigue, place a significant burden on individuals and communities recovering from an outbreak. C. burnetii must manipulate host cell processes in order to promote infection. Our results establish a link between host cell lipid transport processes and C. burnetii’s avoidance of cholesterol toxicity during infection of alveolar macrophages. Elucidating the mechanisms behind bacterial manipulation of the host will yield insight for new strategies to combat this intracellular pathogen.
One Hundred Times Better, at Home in Our Own Beds: Implementation of Home Intravenous Hydration After Chemotherapy in Children With Cancer

Background: Home-based cancer care offers new ways of delivering supportive therapies, including post-chemotherapy hydration, traditionally delivered in hospital settings. Understanding how programs are developed and how parents perceive managing care at home offers opportunities to improve services and experiences. Aim: To describe the implementation process and evaluation of a home intravenous hydration program for children with cancer and thus to provide practical information for future initiatives. Methods: Data were prospectively collected on clinical impact, safety indicators, and estimated costs; these were tabulated and analysed. Semi-structured interviews were undertaken with a subset of parents regarding their experience and analysed using content analysis. Results: Over 34 months, 21 children were eligible, and 16 parents were educated and assessed competent with providing home care. All 16 children received home hydration with a median of 5.5 days per child (IQR 6.65 days). This avoided 116 hospital bed-days and associated costs, at an estimated total value of USD $ 105,521, on average saving USD $ 910 per day and USD $ 6,596 per child. There were no adverse events reported, and no child required re-admission to hospital while receiving home hydration. Parents were overwhelmingly positive in their feedback about the program. Verbatim quotes were synthesized under one overarching theme—supporting normality promotes recovery. Conclusion: When adequately trained and well supported, parents highly value providing home-based care to their children. This offers opportunities to improve experiences and outcomes for children and families as well as reduce costs to health services, achieving clinical impact without reducing safety.
The Variable Impact of Clinical Risk-Adjustment Models to Evaluate Hospital Design

Objectives: To identify the impact of clinical risk adjustment models for evaluating pain medication consumption differences between private rooms and a multibed ward. Background: Views of nature are reported to reduce anxiety and pain for patients. This often leads to prioritizing large windows with views for patient rooms; however, it is not clear how other factors influencing pain (e.g., patient demographics) may confound evaluations of room design. Methods: We identified 1,284 patients at the University of Michigan undergoing thyroidectomy where patients recovered in one of the two locations: a private room with a view to nature or a multibed ward with no windows. We used pain medication data from the electronic medical record and risk adjustment models to evaluate pain medication consumption between the room types. Results: Private room patients did not use more pain medications when measured using unadjusted morphine milligram equivalents (18.3 vs. 15.3 mg, p = .06). Risk adjusting for age, gender, comorbidities, opioid history, and procedure subtype resulted in private room patients demonstrating higher consumption of morphine milliequivalents (17.5 vs. 15.5 mg, p < .01). In contrast, risk adjusting for age, gender, opioid history, and selected comorbidities estimated higher pain medication consumption for multibed ward patients relative to private rooms (16.27 vs. 15.51 mg, p < .05). Conclusion: Estimated differences of pain medication consumption for patients in differently designed rooms varied depending on the risk adjustment model. These findings underscore the importance of understanding appropriate clinical measurement and risk adjustment strategies to accurately estimate the impact of design, before applying research into practice.
Effect of size and morphology of functionalized upconversion nanoparticle labeled probe on stem cell absorption

In order to improve the application of stem cell therapy, it is important to monitor the proliferation and differentiation of transplanted stem cells in real time, high sensitivity and high precision. Upconversion nanoparticles (UCNPs) have been employed as bioimaging agents and delivery vehicles for gene therapeutics in several types of cells. Herein, we fabricated multiple functional upconversion nanoparticles (FUC-NPs) as exogenous contrast agents to investigate the effect of FUC-NPs size on the efficiency of tracking human umbilical cord mesenchymal stem cells (HUCMSCs). We used TEM, DLS, MTT, etc. systematically detected the effects of nanoparticle dose and exposure time on HUCMSCs cytotoxicity. Our data showed that incubation of FUC-NPs, HUCMSCs are able to maintain their viability and differentiation ability. Interestingly, the small size FUC-NPs examined, S-FUCs, had a much higher uptake capability than the other FUC-NPs (B-FUCs, H-FUCs and R-FUCs). The study will aid in UCNPs for the engineering of stem cell application in the future.
Health outcomes and service use patterns associated with co‐located outpatient mental health care and alcohol and other drug specialist treatment: A systematic review

Abstract Issues Despite long‐standing recommendations to integrate mental health care and alcohol and other drug (AOD) treatment, no prior study has synthesised evidence on the impact of physically co‐locating these specialist services on health outcomes. Approach We searched Medline, PsycINFO, Embase, Web of Science and CINAHL for studies examining health outcomes associated with co‐located outpatient mental health care and AOD specialist treatment for adults with a dual diagnosis of substance use disorder and mental illness. Due to diversity in study designs, patient populations and outcome measures among the included studies, we conducted a narrative synthesis. Risk of bias was assessed using the MASTER scale. Key Findings Twenty‐eight studies met our inclusion criteria. We found provisional evidence that integrated care that includes co‐located mental health care and AOD specialist treatment is associated with reductions in substance use and related harms and mental health symptom severity, improved quality of life, decreased emergency department presentations/hospital admissions and reduced health system expenditure. Many studies had a relatively high risk of bias and it was not possible to disaggregate the independent effect of physical co‐location from other common aspects of integrated care models such as care coordination and the integration of service processes. Implications There are few high‐quality, peer‐reviewed studies establishing the impact of co‐located mental health care and AOD specialist treatment on health outcomes. Further research is required to inform policy, guide implementation and optimise practice. Conclusion Integrated care that includes the co‐location of mental health care and AOD specialist treatment may yield health and economic benefits.
The moderating role of neighborhood disadvantage on the link between functional limitations and self-rated health

Background Self-rated health is an important health outcome and determinant of health. Improvements to our understanding on self-rated health could help design plans and strategies to improve self-rated health and achieve other preferred health outcomes. This study examined whether the link between functional limitations and self-rated health varies by neighborhood socioeconomic status. Methods This study used the Midlife in the United States study linked with the Social Deprivation Index developed by the Robert Graham Center. Our sample consist of noninstitutionalized middle to older adults in the United States (n = 6,085). Based on stepwise multiple regression models, we computed adjusted odds ratios to examine the relationships between neighborhood socioeconomic status, functional limitations, and self-rated health. Results Respondents in the socioeconomically disadvantaged neighborhoods were older, had higher percentage of females, non-White respondents, lower educational attainment, lower perceived neighborhood quality, and worse health status with greater number of functional limitations than those in socioeconomically advantaged neighborhoods. Results showed a significant interaction was found where neighborhood-level discrepancies in self-rated health was biggest among individuals with highest number of functional limitations (B = -0.28, 95% CI[0.53, -0.04], p = 0.025). Specifically, individuals with the highest number of functional limitations from the disadvantaged neighborhoods had higher self-rated health compared to those from advantaged neighborhoods. Conclusions Our study findings highlight that neighborhood discrepancy in self-rated health is underestimated particularly among those with severe functional limitations. Moreover, when interpreting self-rated health status, values should not be taken face value, and should be considered together with the environmental conditions of where one resides.
The impact of blood pressure variability on cognition: current limitations and new advances

Dementia is the most common neurodegenerative disease in the aging population. Emerging evidence indicates that blood pressure (BP) variability is correlated with cognitive impairment and dementia independent of mean BP levels. The state-of-the-art review summarizes the latest evidence regarding the impact of BP variability on cognition in cognitively intact populations, patients with mild cognitive impairment, and different dementia types, focusing on the important confounding factors and new advances. This review also summarizes the potential mechanisms underlying the relationship between BP variability and cognitive impairment, and dementia, briefly discussing sex differences in the relationship. At last, current limitations and future perspectives are discussed to optimize BP management in preventing cognitive impairment and dementia.
Event-Triggered Multiasynchronous H∞ Control for Markov Jump Systems With Transmission Delay

In this article, the issue of event-triggered multiasynchronous <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> control for Markov jump systems with transmission delay is concerned. In order to reduce sampling frequency, multiple event-triggered schemes (ETSs) are introduced. Then hidden Markov model (HMM) is employed to describe multiasynchronous jumps among subsystems, ETSs, and controller. Based on the HMM, the time-delay closed-loop model is constructed. In particular, when triggered data are transmitted over networks, a large transmission delay may cause disorder of transmission data such that the time-delay closed-loop model cannot be developed directly. To overcome this difficulty, a packet loss schedule is presented and the unified time-delay closed-loop system is obtained. By the use of the Lyapunov–Krasovskii functional method, sufficient conditions with the controller design are formulated for guaranteeing the <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> performance of the time-delay closed-loop system. Finally, the effectiveness of the proposed control strategy is demonstrated by two numerical examples.
Ecien t Inference of Partial Types

Partial types for the -calculus were introduced by Thatte in 1988 [8] as a means of typing objects that are not typable with simple types, such as heterogeneous lists and persistent data. In that paper he showed that type inference for partial types was semidecidable. Decidability remained open until quite recently, when O’Keefe and Wand [5] gave an exponential time algorithm for type inference. In this paper we give an O(n 3 ) algorithm. Our algorithm constructs a certain nite automaton that represents a canonical solution to a given set of type constraints. Moreover, the construction works equally well for recursive types; this solves an open problem stated in [5].
Camera calibration method based on circular points

An easy method for computing a camera internal parameters based on circular points is proposed.The proposed method only requires the camera to observe a planar calibration pattern which includes a circle and a pencil of its diameters,from at least three different orientations,and either the camera or the planar pattern can be moved freely.The motion need not be known,vanishing points and the vanishing line can be determined using the invariant of tangency,circular points can be computed through the intersection of the vanishing line with the ellipse,and then all the five intrinsic parameters can be determined linearly.The whole process needs to know neither any metric measurement on the model plane,nor the correspondences between points on images.Extensive simulations and experimental results with real images show that the proposed technique is both accurate and robust.
Blind Identification and Blind Equalization of MIMO Channels Based on QR Factorization

Traditional blind identification methods for SIMO channels,such as subspace method (SS),etc.,are based on the eigen value decomposition (EVD) or singular value decomposition (SVD) of the received signal's correlation matrix,which may need more data to make the estimation of correlation matrix be accurate.Recently a QR factorization based blind identification algorithm for SIMO channels with good performance and without calculating the correlation matrix is proposed.In this paper,we extend the QR factorization based algorithm for the blind identification of MIMO channels,and we then proved the extended algorithm to be valid for a more generalized case,that is,the source signals are spatially related.Simulations demonstrate that the QR-based identification algorithms for MIMO channels preserves advantages of fast convergence,low computational costs,and robustness to noise.We also compare the performance of the QR-based method with that of traditional MIMO blind identification algorithms.
Topological Characteristics and Vulnerability Analysis of Rural Traffic Network

Rural traffic network (RTN), as a complex network, plays a significant role in the field of resisting natural disasters and emergencies. In this paper, we analyze the vulnerability of RTN via three traffic network models (i.e., No-power Traffic Network Model (NTNM), Distance Weight Traffic Network Model (DWTNM), and Road Level Weight Traffic Network Model (RLWTNM)). Firstly, based on the complex network theory, RTN is constructed by using road mapping method, according to the topological features. Secondly, Random Attack (RA) and Deliberate Attack (DA) strategies are used to analyze network vulnerability in three rural traffic network models. By analyzing the attack tolerance of RTN under the condition of different attack patterns, we find that the road level weight traffic network has a good performance to represent the vulnerability of RTN.
Chemogenetics identifies separate area 25 brain circuits involved in anhedonia and anxiety in marmosets

Poor outcomes are common in individuals with anxiety and depression, and the brain circuits underlying symptoms and treatment responses remain elusive. To elucidate these neural circuits, experimental studies must specifically manipulate them, which is only possible in animals. Here, we used a chemogenetics strategy involving engineered designer receptors exclusively activated by designer drugs (DREADDs) to activate a region of the marmoset brain that is dysfunctional in human patients with major depressive disorder, called the subcallosal anterior cingulate cortex area 25 (scACC-25). Using this DREADDs system, we identified separate scACC-25 neural circuits that underlie specific components of anhedonia and anxiety in marmosets. Activation of the neural pathway connecting the scACC-25 to the nucleus accumbens (NAc) caused blunting of anticipatory arousal (a form of anhedonia) in marmosets in response to a reward-associated conditioned stimulus in an appetitive Pavlovian discrimination test. Separately, activation of the circuit between the scACC-25 and the amygdala increased a measure of anxiety (the threat response score) when marmosets were presented with an uncertain threat (human intruder test). Using the anhedonia data, we then showed that the fast-acting antidepressant ketamine when infused into the NAc of marmosets prevented anhedonia after scACC-25 activation for more than 1 week. These neurobiological findings provide targets that could contribute to the development of new treatment strategies. Description Separate area 25 brain circuits drive reward- and threat-associated responses in nonhuman primates. Dissecting the neural circuitry of depression There is still much to learn about the brain circuits involved in depression and anxiety. Here, Wood and colleagues demonstrate that specific connections of a brain region called area 25 directly affect anxiety and anhedonia in marmosets. Using a chemogenetics strategy, the authors showed that activation of area 25 connections to the nucleus accumbens resulted in anhedonia, whereas activation of area 25 connections to the amygdala induced anxiety in the animals. Moreover, the nucleus accumbens was a target for the response of marmosets to the fast-acting antidepressant ketamine. These findings may help to elucidate more effective treatment strategies for depression and anxiety. —OS