Miracle-dz/UniFAR-FTUs huggingface dataset:
Munificent Environments, Management Control, and the Cost of Rural Hospital Care

Rural hospitals have been threatened by declining revenues. Control over costs will be necessary to help these hospitals survive. Investigation of the determinants of hospital costs in Iowa reveals that costs are primarily caused by environmental factors, rather than variables over which managers have control. Furthermore, efforts by policy makers to improve hospital efficiency by stimulating competition among hospitals may have been ineffective, since the level of competition was not found to be associated with hospital production costs.
Integrity and authenticity of ADS-B broadcasts

We propose a novel approach to provide authenticity and integrity of Automatic Dependent Surveillance-Broadcast (ADS-B) messages. We employ a key-management schema for authentication and rely on a keyed-hashed message authentication code (HMAC) for integrity. Our approach avoids scalability and compatibility issues, as we neither change the packet format nor its size.
Coping with a Nutrient Deficiency: Cultural Models of Vitamin A Deficiency in Northern Niger

Cultural explanations and management strategies for specific signs and symptoms of vitamin A deficiency are explored in a Hausa-speaking community in northern Niger. Their interpretations of the etiology of nightblindness in young children and pregnant women focus on food-related causes, in which “lack of good food” is central. In parallel with the significance of food in the etiology of nightblindness, the recommended treatments are home food remedies, primarily involving liver, meat, or green leaves. The locally attributed etiology for the more severe manifestation of vitamin A deficiency, xerophthalmia, stands in sharp contrast to this. People believe the primary cause is “heat” produced by acute infectious disease (particularly measles). A trip to the medical dispensary or a reliance upon home remedies are the preferred treatment options for this condition. We explore the striking correspondence between local interpretations of nightblindness and contemporary medical knowledge and treatment in relation to the very different explanations and curative measures offered for more serious manifestations of vitamin A deficiency.
Assessment of Area-Level Disease Control and Surveillance Vulnerabilities: An Application to Visceral Leishmaniasis in Brazil

Abstract. The large number of activities contributing to zoonoses surveillance and control capability, on both human and animal domains, and their likely heterogeneous implementation across administrative units make assessment and comparisons of capability performance between such units a complex task. Such comparisons are important to identify gaps in capability development, which could lead to clusters of vulnerable areas, and to rank and subsequently prioritize resource allocation toward the least capable administrative units. Area-level preparedness is a multidimensional entity and, to the best of our knowledge, there is no consensus on a single comprehensive indicator, or combination of indicators, in a summary metric. We use Bayesian spatial factor analysis models to jointly estimate and rank disease control and surveillance capabilities against visceral leishmaniasis (VL) at the municipality level in Brazil. The latent level of joint capability is informed by four variables at each municipality, three reflecting efforts to monitor and control the disease in humans, and one variable informing surveillance capability on the reservoir, the domestic dog. Because of the large volume of missing data, we applied imputation techniques to allow production of comprehensive rankings. We were able to show the application of these models to this sparse dataset and present a ranked list of municipalities based on their overall VL capability. We discuss improvements to our models, and additional applications.
Reliable change in pediatric brain tumor: A preliminary investigation

ABSTRACT Children treated for brain tumor show evidence of declines in general intellectual abilities (i.e., IQ). Group-level data indicate subtle declines over time on average, but no study has utilized a clinical criterion to identify and describe a reliable change in survivors of pediatric brain tumor (PBT). In this study, we discuss the utility of reliable change index (RCI) methodology to supplement group-level analysis (e.g., repeated measures ANOVA). This pilot sample consisted of 22 children (M age = 10.47 years) treated for PBT who completed initial and follow-up assessments (M interval = 23.58 months). Cognitive data included composite scores from the WISC-IV. An RCI z-score was calculated for each participant on each composite score based on two different test–retest reliability coefficients. As a group, survivors of PBT did not demonstrate a statistically significant change from initial to follow-up on any WISC-IV composite score. When RCI was calculated based on reliability coefficients with shorter test–retest intervals provided by the test publisher, 77% of survivors demonstrated a reliable change in performance on at least one measure. The frequency of RCI decreases in working memory was significantly higher than expected. In contrast, only 32% of survivors showed reliable changes on at least one measure when RCI was based on a reliability coefficient derived from a clinical sample with a longer retest interval. This study demonstrates that highly divergent results may be obtained with RCI and the importance of the source of reliability estimates.
Diffusely Decreased Liver Uptake on FDG PET and Cancer-Associated Cachexia With Reduced Survival.

OBJECTIVES We investigated clinical characteristics of patients with extremely increased or decreased physiologic F-FDG uptake of the liver and their prognosis. METHODS One thousand four hundred eighty-seven PET/CT scans of patients with known or suspected malignancy were retrospectively analyzed. A spherical volume of interest (3 cm in diameter) was set on the right lobe of the liver to calculate the SUVmean. Scans with extremely high (SUVmean >97.5th percentile) and low (SUVmean <2.5th percentile) FDG uptake in the liver were evaluated. Physical and laboratory data among a control group (n = 30), the extremely high liver uptake group (HG, n = 36), and the extremely low liver uptake group (LG, n = 36) were compared. Overall survival (OS) of the 3 groups was also compared. RESULTS Body weight and body mass index in the HG (SUVmean ≥3.04) were significantly higher than those in the control group. The LG cases (SUVmean ≤1.78) had anemia, impaired liver function, and systemic inflammation. They were also in a poor nutritional state. The characteristics of LG cases had many things in common with those of cachectic patients. Indeed, 36.1% of LG cases met the diagnostic criteria for cachexia. Moreover, in LG cases with viable and/or recurrent malignant lesions on FDG PET, the proportion of cachexia increased by 52.6%. The OS of LG cases (median, 33 months) was significantly worse than that of controls and HG cases. CONCLUSIONS Our data indicate that cancer patients with extremely decreased liver FDG uptake were likely to have cancer cachexia and a lower OS.
Detection of Epstein-Barr Virus Infection in Non-Small Cell Lung Cancer

Previous investigations proposed a link between the Epstein-Barr virus (EBV) and lung cancer (LC), but the results are highly controversial largely due to the insufficient sample size and the inherent limitation of the traditional viral screening methods such as PCR. Unlike PCR, current next-generation sequencing (NGS) utilizes an unbiased method for the global assessment of all exogenous agents within a cancer sample with high sensitivity and specificity. In our current study, we aim to resolve this long-standing controversy by utilizing our unbiased NGS-based informatics approaches in conjunction with traditional molecular methods to investigate the role of EBV in a total of 1127 LC. In situ hybridization analysis of 110 LC and 10 normal lung samples detected EBV transcripts in 3 LC samples. Comprehensive virome analyses of RNA sequencing (RNA-seq) data sets from 1017 LC and 110 paired adjacent normal lung specimens revealed EBV transcripts in three lung squamous cell carcinoma and one lung adenocarcinoma samples. In the sample with the highest EBV coverage, transcripts from the BamHI A region accounted for the majority of EBV reads. Expression of EBNA-1, LMP-1 and LMP-2 was observed. A number of viral circular RNA candidates were also detected. Thus, we for the first time revealed a type II latency-like viral transcriptome in the setting of LC in vivo. The high-level expression of viral BamHI A transcripts in LC suggests a functional role of these transcripts, likely as long non-coding RNA. Analyses of cellular gene expression and stained tissue sections indicated an increased immune cell infiltration in the sample expressing high levels of EBV transcripts compared to samples expressing low EBV transcripts. Increased level of immune checkpoint blockade factors was also detected in the sample with higher levels of EBV transcripts, indicating an induced immune tolerance. Lastly, inhibition of immune pathways and activation of oncogenic pathways were detected in the sample with high EBV transcripts compared to the EBV-low LC indicating the direct regulation of cancer pathways by EBV. Taken together, our data support the notion that EBV likely plays a pathological role in a subset of LC.
Recent Trends of Foaming in Polymer Processing: A Review

Polymer foams have low density, good heat insulation, good sound insulation effects, high specific strength, and high corrosion resistance, and are widely used in civil and industrial applications. In this paper, the classification of polymer foams, principles of the foaming process, types of blowing agents, and raw materials of polymer foams are reviewed. The research progress of various foaming methods and the current problems and possible solutions are discussed in detail.
Improved Oxygen Supply to Multicellular Spheroids Using A Gas-permeable Plate and Embedded Hydrogel Beads

Culture systems for three-dimensional tissues, such as multicellular spheroids, are indispensable for high-throughput screening of primary or patient-derived xenograft (PDX)-expanded cancer tissues. Oxygen supply to the center of such spheroids is particularly critical for maintaining cellular functions as well as avoiding the development of a necrotic core. In this study, we evaluated two methods to enhance oxygen supply: (1) using a culture plate with a gas-permeable polydimethylsiloxane (PDMS) membrane on the bottom, and; (2) embedding hydrogel beads in the spheroids. Culturing spheroids on PDMS increased cell growth and affected glucose/lactate metabolism and CYP3A4 mRNA expression and subsequent enzyme activity. The spheroids, comprised of 5000 Hep G2 cells and 5000 20 µm-diameter hydrogel beads, did not develop a necrotic core for nine days when cultured on a gas-permeable sheet. In contrast, central necrosis in spheroids lacking hydrogel beads was observed after day 3 of culture, even when using PDMS. These results indicate that the combination of gas-permeable culture equipment and embedded hydrogel beads improves culture 3D spheroids produced from primary or PDX-expanded tumor cells.
Engineering CatM, a LysR-Type Transcriptional Regulator, to Respond Synergistically to Two Effectors

The simultaneous response of one transcriptional regulator to different effectors remains largely unexplored. Nevertheless, such interactions can substantially impact gene expression by rapidly integrating cellular signals and by expanding the range of transcriptional responses. In this study, similarities between paralogs were exploited to engineer novel responses in CatM, a regulator that controls benzoate degradation in Acinetobacter baylyi ADP1. One goal was to improve understanding of how its paralog, BenM, activates transcription in response to two compounds (cis,cis-muconate and benzoate) at levels significantly greater than with either alone. Despite the overlapping functions of BenM and CatM, which regulate many of the same ben and cat genes, CatM normally responds only to cis,cis-muconate. Using domain swapping and site-directed amino acid replacements, CatM variants were generated and assessed for the ability to activate transcription. To create a variant that responds synergistically to both effectors required alteration of both the effector-binding region and the DNA-binding domain. These studies help define the interconnected roles of protein domains and extend understanding of LysR-type proteins, the largest family of transcriptional regulators in bacteria. Additionally, renewed interest in the modular functionality of transcription factors stems from their potential use as biosensors.
Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids

Epidemiological studies indicate that insulin resistance (IR), a hallmark of type 2 diabetes, is associated with an increased risk of major depression. Here, we demonstrated that male mice fed a high-fat diet (HFD) exhibited peripheral metabolic impairments reminiscent of IR accompanied by elevated circulating levels of branched-chain amino acids (BCAAs), whereas both parameters were normalized by chronic treatment with metformin (Met). Given the role of BCAAs in the regulation of tryptophan influx into the brain, we then explored the activity of the serotonin (5-HT) system. Our results indicated that HFD-fed mice displayed impairment in the electrical activity of dorsal raphe 5-HT neurons, attenuated hippocampal extracellular 5-HT concentrations and anxiety, one of the most visible and early symptoms of depression. On the contrary, Met stimulated 5-HT neurons excitability and 5-HT neurotransmission while hindering HFD-induced anxiety. Met also promoted antidepressant-like activities as observed with fluoxetine. In light of these data, we designed a modified HFD in which BCAA dietary supply was reduced by half. Deficiency in BCAAs failed to reverse HFD-induced metabolic impairments while producing antidepressant-like activity and enhancing the behavioral response to fluoxetine. Our results suggest that Met may act by decreasing circulating BCAAs levels to favor serotonergic neurotransmission in the hippocampus and promote antidepressant-like effects in mice fed an HFD. These findings also lead us to envision that a diet poor in BCAAs, provided either alone or as add-on therapy to conventional antidepressant drugs, could help to relieve depressive symptoms in patients with metabolic comorbidities. SIGNIFICANCE STATEMENT Insulin resistance in humans is associated with increased risk of anxiodepressive disorders. Such a relationship has been also found in rodents fed a high-fat diet (HFD). To determine whether insulin-sensitizing strategies induce anxiolytic- and/or antidepressant-like activities and to investigate the underlying mechanisms, we tested the effects of metformin, an oral antidiabetic drug, in mice fed an HFD. Metformin reduced levels of circulating branched-chain amino acids, which regulate tryptophan uptake within the brain. Moreover, metformin increased hippocampal serotonergic neurotransmission while promoting anxiolytic- and antidepressant-like effects. Moreover, a diet poor in these amino acids produced similar beneficial behavioral property. Collectively, these results suggest that metformin could be used as add-on therapy to a conventional antidepressant for the comorbidity between metabolic and mental disorders.
Extracellular Polyphosphate Promotes Macrophage and Fibrocyte Differentiation, Inhibits Leukocyte Proliferation, and Acts as a Chemotactic Agent for Neutrophils

Key Points Polyphosphate released from platelets induces fibrocyte differentiation. Polyphosphate can act as a chemoattractant for neutrophils. Fibrocytes are monocyte-derived fibroblast like cells that participate in wound healing, but little is known about what initiates fibrocyte differentiation. Blood platelets contain 60–100-mer polymers of phosphate groups called polyphosphate, and when activated, platelets induce blood clotting (the first step in wound healing) in part by the release of polyphosphate. We find that activated platelets release a factor that promotes fibrocyte differentiation. The factor is abolished by treating the crude platelet factor with the polyphosphate-degrading enzyme polyphosphatase, and polyphosphate promotes fibrocyte differentiation. Macrophages and recruited neutrophils also potentiate wound healing, and polyphosphate also promotes macrophage differentiation and induces chemoattraction of neutrophils. In support of the hypothesis that polyphosphate is a signal that affects leukocytes, we observe saturable binding of polyphosphate to these cells. Polyphosphate also inhibits leukocyte proliferation and proteasome activity. These results suggest new roles for extracellular polyphosphate as a mediator of wound healing and inflammation and also provide a potential link between platelet activation and the progression of fibrosing diseases.
Proteomic Analyses of Mammary Glands Provide Insight into the Immunity and Metabolism Pathways Associated with Clinical Mastitis in Meat Sheep

Simple Summary Clinical mastitis is one of the most common diseases in sheep and is of major economic concern due to treatment costs, inadequate lamb growth and premature eliminate of ewes. To preliminarily explore possible regulatory roles of proteins involved in the host-pathogen interactions during intramammary infection triggered by this disease in meat sheep, mammary tissues were harvested from sheep with healthy and clinical mastitis caused by natural infection, and the differentially expressed proteins were identified in an infected group when compared to a healthy group, using comparative proteomics based on two-dimensional electrophoresis. Further enrichment analyses indicated that most of the differentially expressed proteins mainly engaged in regulating immune responses and metabolisms. These findings offer candidate proteins for further studies on molecular mechanisms of host defense response and metabolism in sheep cases. Abstract Clinical mastitis is still an intractable problem for sheep breeding. The natural immunologic mechanisms of the mammary gland against infections are not yet understood. For a better understanding of the disease-associated proteins during clinical mastitis in meat sheep, we performed two-dimensional electrophoresis (2-DE)-based comparative proteomic analyses of mammary tissues, including from healthy mammary tissues (HMTs) and from mammary tissues with clinical mastitis (CMMTs). The 2-DE results showed that a total of 10 up-regulated and 16 down-regulated proteins were identified in CMMTs when compared to HMTs. Of these, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses revealed that most proteins were associated with immune responses or metabolisms. The results of qRT-PCR and Western blot for randomly selected four differentially expressed proteins (DEPs) including superoxide dismutase [Mn] (SOD2), annexin A2 (ANAX2), keratin 10 (KRT10) and endoplasmic reticulum resident protein 29 (ERP29) showed that their expression trends were consistent with 2-DE results except ANXA2 mRNA levels. This is an initial report describing the 2-DE-based proteomics study of the meat sheep mammary gland with clinical mastitis caused by natural infection, which provides additional insight into the immune and metabolic mechanisms during sheep mastitis.
Beta‐cell excitability and excitability‐driven diabetes in adult Zebrafish islets

Islet β‐cell membrane excitability is a well‐established regulator of mammalian insulin secretion, and defects in β‐cell excitability are linked to multiple forms of diabetes. Evolutionary conservation of islet excitability in lower organisms is largely unexplored. Here we show that adult zebrafish islet calcium levels rise in response to elevated extracellular [glucose], with similar concentration–response relationship to mammalian β‐cells. However, zebrafish islet calcium transients are nor well coupled, with a shallower glucose‐dependence of cytoplasmic calcium concentration. We have also generated transgenic zebrafish that conditionally express gain‐of‐function mutations in ATP‐sensitive K+ channels (KATP‐GOF) in β‐cells. Following induction, these fish become profoundly diabetic, paralleling features of mammalian diabetes resulting from equivalent mutations. KATP‐GOF fish become severely hyperglycemic, with slowed growth, and their islets lose glucose‐induced calcium responses. These results indicate that, although lacking tight cell‐cell coupling of intracellular Ca2+, adult zebrafish islets recapitulate similar excitability‐driven β‐cell glucose responsiveness to those in mammals, and exhibit profound susceptibility to diabetes as a result of inexcitability. While illustrating evolutionary conservation of islet excitability in lower vertebrates, these results also provide important validation of zebrafish as a suitable animal model in which to identify modulators of islet excitability and diabetes.
Implementation of an opioid weaning protocol to improve pain management, and to prevent or decrease iatrogenic withdrawal syndrome in the neonatal intensive care.

AIM The aim of this evidence implementation project was to improve pain assessment and management of the neonate receiving an opioid infusion, and to prevent or decrease the incidence of iatrogenic withdrawal syndrome (IWS). METHODS The current project was carried out in two intensive care areas of a 79 bed tertiary Neonatal Unit in Australia. A pre/postaudit design was utilized. Patient charts were reviewed to collect baseline audit data on pain assessments and titration of opioids. A weaning protocol was developed and implemented along with targeted staff education to align current practice with best practice recommendations. A postimplementation audit was then conducted to evaluate changes in practice. RESULTS A total of 32 charts (13 pre/19 post) were reviewed to evaluate pain assessment, titration of opioids, and the identification of any signs and symptoms of IWS. The results demonstrated an improvement in the completion of pain assessments by 34%, and 100% compliance to withdrawal assessment following the introduction of an IWS assessment tool. For neonates receiving analgesics for less than 4 days, adherence to the weaning schedule occurred in 75%. No clinical signs of IWS were seen in this cohort. For neonates receiving analgesics for greater than 4 days, adherence to the weaning schedule occurred in only 55%. Of those neonates where the protocol was not followed, 67% developed clinical signs of IWS. CONCLUSION Although this project demonstrated improvements in pain assessment and the identification of IWS, lack of adherence to the pain management policy and weaning tool has increased awareness of the importance of collaboration within the multidisciplinary team to improve outcomes. Several barriers were identified prior to implementation and various methods were employed to overcome these. Despite this, consistency of practice and change-management remain a challenge in clinical care.