Miracle-dz/UniFAR-FTUs huggingface dataset:
Quiet Time Improves the Patient Experience

Supplemental Digital Content is Available in the Text. Background: A quiet environment promotes rest and healing but is often challenging to provide in a busy acute care setting. Improving quiet in the hospital for designated hours improves patient satisfaction. Such efforts have typically been the primary responsibility of the nursing staff. Local Problem: Two medical units with consistently low Hospital Consumer Assessment of Health Care Providers and Systems (HCAHPS) “always quiet” scores were chosen for this study. Methods: A multidisciplinary team used Lean methods and the Model for Improvement to test interventions for quiet time (QT) and used HCAHPS “always quiet” scores as the primary outcome measure. Interventions: The team instituted nighttime and afternoon QT supported by rounding and scripting, dimming lights, lowering staff voices, offering a sleep menu at night, and replacing noisy wheels. Results: Quiet scores improved on both units after 11 months. Conclusions: Noise in hospitals is often beyond the scope of nurse-driven improvement; however, a QT protocol led by nurses, developed by multiple stakeholders, and focused on changing expectations for quiet can lead to measurable improvements in patient perception of quiet.
The Diurnal Timing of Starvation Differently Impacts Murine Hepatic Gene Expression and Lipid Metabolism – A Systems Biology Analysis Using Self-Organizing Maps

Organisms adapt their metabolism and draw on reserves as a consequence of food deprivation. The central role of the liver in starvation response is to coordinate a sufficient energy supply for the entire organism, which has frequently been investigated. However, knowledge of how circadian rhythms impact on and alter this response is scarce. Therefore, we investigated the influence of different timings of starvation on global hepatic gene expression. Mice (n = 3 each) were challenged with 24-h food deprivation started in the morning or evening, coupled with refeeding for different lengths and compared with ad libitum fed control groups. Alterations in hepatocyte gene expression were quantified using microarrays and confirmed or complemented with qPCR, especially for lowly detectable transcription factors. Analysis was performed using self-organizing maps (SOMs), which bases on clustering genes with similar expression profiles. This provides an intuitive overview of expression trends and allows easier global comparisons between complex conditions. Transcriptome analysis revealed a strong circadian-driven response to fasting based on the diurnal expression of transcription factors (e.g., Ppara, Pparg). Starvation initiated in the morning produced known metabolic adaptations in the liver; e.g., switching from glucose storage to consumption and gluconeogenesis. However, starvation initiated in the evening produced a different expression signature that was controlled by yet unknown regulatory mechanisms. For example, the expression of genes involved in gluconeogenesis decreased and fatty acid and cholesterol synthesis genes were induced. The differential regulation after morning and evening starvation were also reflected at the lipidome level. The accumulation of hepatocellular storage lipids (triacylglycerides, cholesteryl esters) was significantly higher after the initiation of starvation in the morning compared to the evening. Concerning refeeding, the gene expression pattern after a 12 h refeeding period largely resembled that of the corresponding starvation state but approached the ad libitum control state after refeeding for 21 h. Some components of these regulatory circuits are discussed. Collectively, these data illustrate a highly time-dependent starvation response in the liver and suggest that a circadian influence cannot be neglected when starvation is the focus of research or medicine, e.g., in the case of treating victims of sudden starvation events.
Human Endogenous Retroviruses Are Ancient Acquired Elements Still Shaping Innate Immune Responses

About 8% of our genome is composed of sequences with viral origin, namely human Endogenous Retroviruses (HERVs). HERVs are relics of ancient infections that affected the primates' germ line along the last 100 million of years, and became stable elements at the interface between self and foreign DNA. Intriguingly, HERV co-evolution with the host led to the domestication of activities previously devoted to the retrovirus life cycle, providing novel cellular functions. For example, selected HERV envelope proteins have been coopted for pregnancy-related purposes, and proviral Long Terminal Repeats participate in the transcriptional regulation of various cellular genes. Given the HERV persistence in the host genome and its basal expression in most healthy tissues, it is reasonable that human defenses should prevent HERV-mediated immune activation. Despite this, HERVs and their products (including RNA, cytosolic DNA, and proteins) are still able to modulate and be influenced by the host immune system, fascinatingly suggesting a central role in the evolution and functioning of the human innate immunity. Indeed, HERV sequences had been major contributors in shaping and expanding the interferon network, dispersing inducible genes that have been occasionally domesticated in various mammalian lineages. Also the HERV integration within or near to genes encoding for critical immune factors has been shown to influence their activity, or to be responsible for their polymorphic variation in the human population, such as in the case of an HERV-K(HML10) provirus in the major histocompatibility complex region. In addition, HERV expressed products have been shown to modulate innate immunity effectors, being therefore often related on the one side to inflammatory and autoimmune disorders, while on the other side to the control of excessive immune activation through their immunosuppressive properties. Finally, HERVs have been proposed to establish a protective effect against exogenous infections. The present review summarizes the involvement of HERVs and their products in innate immune responses, describing how their intricate interplay with the first line of human defenses can actively contribute either to the host protection or to his damage, implying a subtle balance between the persistence of HERV expression and the maintenance of a basal immune alert.
Dynamic Compositionality in Recursive Neural Networks with Structure-aware Tag Representations

Most existing recursive neural network (RvNN) architectures utilize only the structure of parse trees, ignoring syntactic tags which are provided as by-products of parsing. We present a novel RvNN architecture that can provide dynamic compositionality by considering comprehensive syntactic information derived from both the structure and linguistic tags. Specifically, we introduce a structure-aware tag representation constructed by a separate tag-level tree-LSTM. With this, we can control the composition function of the existing wordlevel tree-LSTM by augmenting the representation as a supplementary input to the gate functions of the tree-LSTM. In extensive experiments, we show that models built upon the proposed architecture obtain superior or competitive performance on several sentence-level tasks such as sentiment analysis and natural language inference when compared against previous tree-structured models and other sophisticated neural models.
Enhanced Expression of TGFBI Promotes the Proliferation and Migration of Glioma Cells

Background/Aims: Transforming growth factor beta-induced protein (TGFBI) is an extracellular matrix protein induced by TGF-β. Previous studies have reported that the abnormal expression of TGFBI is related to the occurrence and development of some types of cancers, while the role of TGFBI in glioma is uncertain. Methods: The association between TGFBI expression and the prognosis of patients with glioma was analyzed based on data obtained from The Cancer Genome Atlas database. TGFBI expression was analyzed in 3 normal human brains and 57 cases of human gliomas by immunohistochemistry followed by an evaluation of the relationships between TGFBI expression and clinic-pathological features. Furthermore, the RNA interference plasmid pSUPER-shTGFBI was constructed and transfected into U87 and U251 cells to explore the effect of short hairpin RNA against TGFBI (shTGFBI) on cell proliferation, migration, invasion and apoptosis. Western blot analysis was performed to examine the expression of proteins related to apoptosis and proteins in the PI3K/Akt signaling pathway. Results: High TGFBI expression was found to be associated with poor prognosis in patients with glioblastoma multiforme. Immunohistochemistry showed that TGFBI expression was significantly higher in glioma tissue than in normal human brain tissues. The expression level of TGFBI showed no significant correlation with age, sex, lymph-node metastasis, or pathological grade. sh-TGFBI could inhibit proliferation, invasion and migration and induce apoptosis in U87 and U251 cells in vitro. Furthermore, the phosphorylation levels of AKT and mTOR declined significantly in sh-TGFBI transfected U81 and U251 cells when compared with control. Conclusion: TGFBI was up-regulated in glioma cells and played a promoting role in the growth and motility of U87 and U251 cells. These results suggested that TGFBI has the potential to be a diagnostic marker and to serve as a target for the treatment of gliomas.
Behavioral Inhibition and Activation Systems, and Emotional Regulation in Individuals With Chronic Musculoskeletal Pain

Gray's Reinforcement Sensitivity Theory postulates two distinct neurophysiological systems that underlie thoughts, emotions, and behavior: the Behavioral Inhibition System (BIS) and the Behavioral Approach System (BAS). Preliminary research suggests that both systems may play relevant roles in the adjustment of individuals with chronic pain. However, there is a lack of research on the extent to which emotional regulation (i.e., cognitive reappraisal and expressive suppression) mediates the associations between BIS and BAS activation and emotional responses in individuals with chronic pain. The aim of this study was to test a model of the associations between the BIS and BAS, cognitive reappraisal and expressive suppression, and positive and negative affect in individuals with chronic musculoskeletal pain. In total, 516 participants were interviewed. Structural Equation Modeling was used to estimate the associations between variables. The empirical model showed a good fit to the data (χ2/df = 1.95; RMSEA = 0.04; GFI = 0.99; AGFI = 0.98; CFI = 0.99). The hypothesized model received partial support. The BIS was associated with cognitive reappraisal and expressive suppression; cognitive reappraisal was associated with negative and positive affect; expressive suppression was positively associated with affect; and the BAS was not associated with the emotional regulation strategies assessed. However, the BIS and BAS were both directly associated with negative and positive affect. The results suggest that individuals with chronic pain with higher BIS activation appear to use greater expressive suppression. Cognitive reappraisal strongly mediated the BIS-negative affect association. The results also suggest that BAS activation may have a weak or inconsistent association with emotional regulation approaches in individuals with chronic pain. These data provide new and relevant information on the potential role of the BIS and BAS as predictors of psychological functioning in individuals with chronic pain. They suggest that the BIS-BAS model of chronic pain may need to be modified to take into account the potential negative effects of BAS activation. The findings suggest that treatments for emotional regulation could potentially reduce the negative impact of chronic pain via BIS.
Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells

Among the most promising therapeutic modalities for cancer treatment is the blockade of immune checkpoint pathways, which are frequently co-opted by tumors as a major mechanism of immune escape. CTLA-4 and PD-1 are the representative examples, and their blockade by therapeutic antibodies leads to enhanced anti-tumor immunity with durable clinical responses, but only in a minority of patients. This has highlighted the need to identify and target additional immune checkpoints that can be exploited to further enhance immune responses to refractory cancers. These emerging targets include natural killer (NK) cell-directed checkpoint receptors (KIR and CD94/NKG2A) as well as the NK- and T cell-expressed checkpoints TIM-3, TIGIT, CD96, and LAG-3. Interestingly, the potentiation of anti-tumor immunity by checkpoint blockade relies not only on T cells but also on other components of the innate immune system, including NK cells. NK cells are innate lymphoid cells that efficiently kill tumor cells without MHC specificity, which is complementary to the MHC-restricted tumor lysis mediated by cytotoxic T cells. However, the role of these immune checkpoints in modulating the function of NK cells remains unclear and somewhat controversial. Unraveling the mechanisms by which these immune checkpoints function in NK cells and other immune cells will pave the way to developing new therapeutic strategies to optimize anti-tumor immunity while limiting cancer immune escape. Here, we focus on recent findings regarding the roles of immune checkpoints in regulating NK cell function and their potential application in cancer immunotherapy.
Childhood respiratory allergies and symptoms in highly polluted area of Central Europe

ABSTRACT The study investigated the associations between the prevalence of the childhood respiratory diseases and the long-term exposure to air pollution in the burdened area of Moravian–Silesian Region in the Czech Republic. The health data were collected during 2014 in 7,239 children 5, 9, 13 and 17 years of age. Exposure to PM10 and NO2 in the residence addresses was based on dispersion models and GIS based traffic-related indicators. PM10 levels were positively associated with both lifetime (OR 1.35; 95%CI 1.09–1.67) and current (OR 1.32; 95%CI 1.05–1.67) allergic rhinitis; current asthma was associated negatively. The associations between traffic indicator and respiratory health were not found. On the other hand, marked positive associations were found between the respiratory diseases and symptom severity structured into ordinal variables, and PM10 and NO2. Modelled long-term exposure to air pollution was associated with childhood allergic rhinitis and deterioration of the respiratory symptoms.
Viral infections in the biologic therapy era

ABSTRACT Introduction: The development of biologic therapies for treating patients with rheumatic, hematologic, or oncological diseases has increased in the last few years, spreading their use in clinical practice. Areas covered: Clinical experience has evidenced substantial risks for some viral infections and/or reactivations such as viral hepatitis, herpetic infections, and other viruses, as a consequence of specific immune pathway blockages. Biological therapies produce a variable risk of reactivation of viral infections, which is particularly uncertain in the case of the most recently introduced agents. Here we make an extensive review of the viral infections associated with the use of biological drugs and provide a series of recommendations for its prevention and management. Expert commentary: To prevent these infections/reactivations, the practitioner must be aware of the infection-risk profile, performing accurate screening during and after the use of any biologic agent. In some instances, expert recommendations are made for some therapies, while in other scenarios recommendations have not yet been defined making experimental and clinical research an essential approach to elucidate multiple issues yet not resolved in this field.
HIV Antiretroviral Pre‐Exposure Prophylaxis: Development Challenges and Pipeline Promise

The US Food and Drug Administration (FDA) approved oral daily tenofovir/emtricitabine (Truvada) for pre‐exposure prophylaxis of human immunodeficiency virus (HIV) infection in 2012 on the basis of two randomized controlled trials (RCTs), one in men who have sex with men (MSM) and another in HIV serodiscordant heterosexual couples. Subsequently, even greater efficacy has been demonstrated in MSM with rapid population‐level incidence reductions in some locations. In contrast, studies of antiretroviral pre‐exposure prophylaxis (PrEP) in heterosexual women showed only modest or no efficacy, largely attributed to low adherence. The mixed results of antiretroviral‐based PrEP bear witness to unique drug development challenges at this complicated intersection of sexual behavior, public health, and drug development. Multiple innovative methods and formulation strategies followed to address unmet medical needs of persons struggling with daily oral PrEP adherence or preference for nonsystemic PrEP options. Clinical pharmacology plays essential roles throughout this PrEP development process, especially in early product development and through pharmacologically informed enhancement and interpretation of clinical trials.
Five weeks of immersive reminiscence therapy improves autobiographical memory in Alzheimer’s disease

ABSTRACT We examined the effects of a new Immersive Reminiscence Therapy (IRT) programme on cognitive function, including autobiographical memory, in a sample Alzheimer’s disease (AD) patients. A total of 43 AD patients with mild to moderate disease severity were randomly assigned to either an intervention group (n = 22, MMMSE = 20.77), or a control group (n = 21, MMMSE = 19.24). The intervention group received one weekly group-based session of IRT for five weeks in an authentic 1950s style museum environment, matching the time of the participants’ youth. IRT included semi-structured conversations about the past. The control group received standard care. We assessed performance on cognitive function and autobiographical memory at baseline and post-intervention. Five weeks of IRT enhanced subsequent autobiographical memory performance, when participants were cued by concrete objects dated to their youth. Object-cued memories reported post intervention included a significantly higher degree of episodic details and higher word counts. The intervention showed no effect on the Autobiographical Memory Interview or word-cued recall. Global cognitive function and semantic autobiographical memory performance increased across time for both groups. Our findings demonstrate that immersion into a setting, rich on concrete cues dated to the participants’ youth can improve autobiographical remembering.
A synthetic enzymatic pathway for extremely thermophilic acetone production based on the unexpectedly thermostable acetoacetate decarboxylase from Clostridium acetobutylicum

One potential advantage of an extremely thermophilic metabolic engineering host (T opt ≥ 70°C) is facilitated recovery of volatile chemicals from the vapor phase of an active fermenting culture. This process would reduce purification costs and concomitantly alleviate toxicity to the cells by continuously removing solvent fermentation products such as acetone or ethanol, a process we are calling “bio‐reactive distillation. ” Although extremely thermophilic heterologous metabolic pathways can be inspired by existing mesophilic versions, they require thermostable homologs of the constituent enzymes if they are to be utilized in extremely thermophilic bacteria or archaea. Production of acetone from acetyl‐CoA and acetate in the mesophilic bacterium Clostridium acetobutylicum utilizes three enzymes: thiolase, acetoacetyl‐CoA: acetate CoA transferase (CtfAB), and acetoacetate decarboxylase (Adc). Previously reported biocatalytic pathways for acetone production were demonstrated only as high as 55°C. Here, we demonstrate a synthetic enzymatic pathway for acetone production that functions up to at least 70°C in vitro, made possible by the unusual thermostability of Adc from the mesophile C. acetobutylicum, and heteromultimeric acetoacetyl‐CoA:acetate CoA‐transferase (CtfAB) complexes from Thermosipho melanesiensis and Caldanaerobacter subterraneus, composed of a highly thermostable α‐subunit and a thermally labile β‐subunit. The three enzymes produce acetone in vitro at temperatures of at least 70°C, paving the way for bio‐reactive distillation of acetone using a metabolically engineered extreme thermophile as a production host.
Antimalarial bednet protection of children disappears when shared by three or more people in a high transmission setting of western Kenya

Abstract A sizeable proportion of households is forced to share single long-lasting insecticide treated net (LLIN). However, the relationship between increasing numbers of people sharing a net and the risk for Plasmodium infection is unclear. This study revealed whether risk for Plasmodium falciparum infection is associated with the number of people sharing a LLIN in a holoendemic area of Kenya. Children ⩽5 years of age were tested for P. falciparum infection using polymerase chain reaction. Of 558 children surveyed, 293 (52.5%) tested positive for parasitaemia. Four hundred and fifty-eight (82.1%) reported sleeping under a LLIN. Of those, the number of people sharing a net with the sampled child ranged from 1 to 5 (median = 2). Children using a net alone or with one other person were at lower risk than non-users (OR = 0.29, 95% CI 0.10–0.82 and OR = 0.47, 95% CI 0.22–0.97, respectively). On the other hand, there was no significant difference between non-users and children sharing a net with two (OR = 0.88, 95% CI 0.44–1.77) or more other persons (OR = 0.75, 95% CI 0.32–1.72). LLINs are effective in protecting against Plasmodium infection in children when used alone or with one other person compared with not using them. Public health professionals should inform caretakers of the risks of too many people sharing a net.
Gay Midlife Men’s Intergenerational and Interpersonal (Non)Accommodation in the Negotiation of HIV Infection Risk: Implications for Sexual Vitality, Generational Distinctiveness, and Self-Preservation

ABSTRACT This study utilizes interview data and a communication accommodation framework to explore how early midlife gay men negotiate HIV infection risk vis-à-vis a younger gay male sexual culture that has evolved in terms of its regard for dangers associated with HIV infection. Analysis of face-to-face interviews with 33 gay men (aged 40–53) in four U.S. cities revealed a model of gay intergenerational sexual (non)accommodation. The model includes forms of communicative convergence and nonaccommodating behavior that serve some men’s achievement or continuation of sexual vitality and/or positive generational distinctiveness. Similarities and extensions to communication accommodation theory are discussed, as are the model’s implications for understanding some gay men’s management of sexual health at midlife.