Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of depression, anxiety, and stress symptoms on response to cognitive behavioral therapy for insomnia in patients with comorbid insomnia and sleep apnea: a randomized controlled triall.

STUDY OBJECTIVES Patients with comorbid insomnia and sleep apnea (COMISA) report increased severity of depression, anxiety, and stress symptoms compared to patients with either insomnia or sleep apnea alone. Although cognitive behavioral therapy for insomnia (CBTi) is an effective treatment for COMISA, previous research suggests a reduced response to CBTi by insomnia patients with depression, anxiety, and stress symptoms. Therefore, we used RCT data to investigate the impact of depression, anxiety, and stress symptoms before treatment on changes in insomnia after CBTi versus control in patients with COMISA. METHODS 145 patients with COMISA (ICSD-3 insomnia, apnea-hypopnea index ≥ 15 events/h), were randomized to CBTi (n = 72), or no-treatment control (n = 73). One-week sleep diaries and standardized questionnaire measures of insomnia, sleepiness, fatigue, depression, anxiety, and stress were completed pre-treatment and post-treatment. Mixed models were used to examine interactions between depression, anxiety, and stress symptoms before treatment, intervention-group (CBTi, control), and time (pre-, post-treatment) on insomnia symptoms. RESULTS Approximately half of this COMISA sample reported at least mild symptoms of depression (57%), anxiety (53%), and stress (48%) before treatment. Patients reporting greater depression, anxiety, and stress symptoms before treatment also reported increased severity of insomnia, daytime fatigue, and sleepiness. Improvements in questionnaire and diary-measured insomnia symptoms improved during CBTi, and were not moderated by severity of depression, anxiety, or stress symptoms before treatment (all interaction p ≥ 0.11). CONCLUSIONS We found no evidence that symptoms of depression, anxiety, or stress impair the effectiveness of CBTi in improving insomnia symptoms in patients with COMISA. Patients with COMISA and comorbid symptoms of depression, anxiety and stress should be referred for CBTi to treat insomnia and improve subsequent management of their OSA. CLINICAL TRIAL REGISTRATION Registry: Australian New Zealand Clinical Trials Registry, title: Treating comorbid insomnia with obstructive sleep apnoea (COMSIA) study: A new treatment strategy for patients with combined insomnia and sleep apnoea, identifier: ACTRN12613001178730, URL: https://www.anzctr. org.au/Trial/Registration/TrialReview.aspx? id=365184.
Disharmony of the world’s island floras

Disharmony is a key concept in island biology that describes the biased representation of higher taxa on islands compared to their mainland source regions. Although differential colonization success of taxa is predicted by selective dispersal, environmental and biotic filtering, the empirical evidence for disharmony remains largely anecdotal. Here, we develop a novel method for delineating island source regions and present the first global quantitative assessment of island disharmony. We analyzed the overall compositional bias of 320 island floras and examined the over- or under-representation on islands for 450 plant families. We found that the compositional bias of island floras is strongly predicted by geographical and climatic island characteristics (isolation, area, geologic origin, temperature, precipitation), whereas the representation of individual families is only weakly related to family-specific characteristics (family size, family age, taxonomic group, functional traits), indicating that the taxonomic scope of the disharmony concept has historically limited its wider applicability. Our results provide a strong foundation for integrating disharmony with quantitative functional and phylogenetic approaches in order to gain a deeper understanding of assembly processes on islands.
Effect of Cooking Duration on Chemical Composition and Degradation Characteristics of Rattle Box ( Crotalaria retusa ) Seed using In Sacco Technique

Three ruminally fistulated Yankasa rams were used to study the effect of cooking duration on chemical composition and degradation characteristics of rattle box ( Crotalaria retusa ) seeds using the in sacco degradability method. Crotalaria retusa seeds were subjected to cooking time of 0, 15, 30, and 45 minutes, respectively. Four concentrate diets containing Crotalaria retusa seed meal cooked at 0, 15, 30 and 45 minutes were used for this study at incubation periods 3, 6, 12, 24, 36, and 48 hours. The proximate composition showed that duration of cooking had effect on most of the parameters. The CP contents were 20.60, 21.57, 23.97 and 21.97% for 0, 15, 30, and 45 minutes cooking duration, respectively. All the antinutritional factors analysed showed a decrease with increases in cooking time. Phytate showed a decrease with increase in cooking time from 7.31 to 3.22 at 0 to 45 minutes cooking duration, respectively. The result showed a similar pattern for rate of degradation at 6, 12, 24, 36 and 48 hours incubation time with 45 minutes cooking duration significantly (P<0.05) recorded the highest values of 47.00, 54.67, 73.00, 87.00, 90.67 and 93.00 percent disappearance of the experimental feed, respectively. The highest degradability (a+b) was in 0 minutes cooking duration, which was significantly (P<0.05) higher than in 15 and 30 minutes cooking. The rate of degradation constant (c) was significantly (P<0.05) lower in 0, 15 and 30 minutes cooking duration as compared to 45 minutes cooking duration. Effective dry matter degradation significantly (P<0.05) decreased with cooking duration in out flow rate (k). It can be concluded from this study that, cooking duration affects degradation characteristics of C. retusa seeds. Keywords: Crotalaria retusa seed, cooking duration, in sacco, rumen degradation
Oral clade C SHIV challenge models to study pediatric HIV-1 infection by breastmilk transmission

Nonhuman primate (NHP) models are invaluable for HIV pathogenesis, intervention and cure studies. To enhance the translational potential of NHP HIV vaccine studies, clinically relevant R5-tropic, tier 2 neutralization sensitive, and mucosally transmissible simian-human immunodeficiency viruses (SHIVs) have been designed. Towards our goal of developing vaccines to prevent breastmilk transmission of HIV, we evaluated virological outcomes of three distinct SHIVs in repeated weekly oral exposure regimens in infant rhesus macaques. The selected strains SHIV-1157ipd3N4, SHIV-1157(QNE)Y173H, and SHIV CH505 375H.dCT express a clade C HIV Env, the clade most prevalent in regions with high pediatric HIV infections. All three SHIVs were orally transmissible. However, compared to the pediatric SIVmac251 model, SHIV replication was more attenuated. Some animals exposed to weekly low-dose (20 TCID50) SHIV-1157ipd3N4 had transient viremia blips associated with lack or delayed seroconversion. Animals with acute viremia ≥10,000 viral RNA copies/ml seroconverted. This finding was reminiscent of an earlier study suggesting to continue challenges until a threshold of ≥10,000 viral RNA copies/ml is surpassed to achieve seroconversion, one criterion of HIV diagnosis. All animals exposed weekly with higher doses (>104 TCID50) of SHIV-1157(QNE)Y173H or SHIV CH505 375h.dCT developed persistent infection with high peak viremia and seroconverted. Chronic viremia varied widely in all three SHIV infection models. Thus, although R5 clade C SHIVs are excellent tools to study prevention of virus acquisition, secondary virological outcomes of vaccine efficacy (e.g. risk of infection per exposure, modulation of peak viremia, viral set point) will require careful consideration and validation in SHIV challenge models. IMPORTANCE The development of an effective HIV vaccine remains a top priority towards the goal of reducing the number of new HIV infections. Studies in nonhuman primate models of HIV infection have been instrumental in the preclinical evaluation of candidate vaccines. To assess the role of HIV Env-specific antibodies with broadly neutralizing or Fc-mediated effector function in these NHP models, the development and optimization of novel SHIV challenge models is required. We evaluate three different clade C HIV Env SHIVs for infectivity of infant macaques by the oral route. Our results demonstrate that SHIV-1157ipd3N4, SHIV-1157(QNE)Y173H, and SHIV CH505 375H.dCT can be orally transmitted and establish persistent infection in infant rhesus macaques, but chronic viremia levels vary widely. Therefore, SHIV infection models are most pertinent when prevention of systemic infection is the primary readout of vaccine efficacy, but secondary outcome measures of vaccine efficacy will require stringent criteria and extensive validation.
Assessment of cognitive performances in major depressed patients: a 6-month follow-up study

Abstract Objective Our study aimed to assess the longitudinal change of cognitive functions in depressed patients after a 6-month interval free of mood symptoms. Methods In a longitudinal study, 65 patients diagnosed with recurrent major depressive disorder were evaluated twice with neurocognitive tests, during an acute depressed episode and after 6 months of euthymia. The cognitive dimension was assessed with neuropsychological tests of attention and processing speed, memory, verbal fluency, psychomotor speed and executive functions. The severity of depression was evaluated through Hamilton Depression Rating Scale − 17 items. All the results were compared with the outcomes of 35 healthy controls, both in depression and euthymia. Results Depressed patients compared to controls displayed significant statistical differences for most cognitive tests applied, verbal and working memory being the most severely impaired. They were still impaired at the second evaluation. Significant differences were noted between the euthymic and control group, too. Between the depression phase and euthymia, patients obtained significant improvement for attention and processing speed, verbal fluency, motor speed and executive functions. Conclusions Results from the current study indicate that cognitive impairment is more severe for depressed patients, decreases for euthymic subjects, and lasts longer after depressive symptoms remit.
Long Noncoding RNA HOXA11-AS Modulates the Resistance of Nasopharyngeal Carcinoma Cells to Cisplatin via miR-454-3p/c-Met

To elucidate the mechanism of action of HOXA11-AS in modulating the cisplatin resistance of nasopharyngeal carcinoma (NPC) cells. HOXA11-AS and miR-454-3p expression in NPC tissue and cisplatin-resistant NPC cells were measured via quantitative reverse transcriptase polymerase chain reaction. NPC parental cells (C666-1 and HNE1) and cisplatin-resistant cells (C666-1/DDP and HNE1/DDP) were transfected and divided into different groups, after which the MTT method was used to determine the inhibitory concentration 50 (IC50) of cells treated with different concentrations of cisplatin. Additionally, a clone formation assay, flow cytometry and Western blotting were used to detect DDP-induced changes. Thereafter, xenograft mouse models were constructed to verify the in vitro results. Obviously elevated HOXA11-AS and reduced miR-454-3p were found in NPC tissue and cisplatin-resistant NPC cells. Compared to the control cells, cells in the si-HOXA11-AS group showed sharp decreases in cell viability and IC50, and these results were reversed in the miR-454-3p inhibitor group. Furthermore, HOXA11-AS targeted miR-454-3p, which further targeted c-Met. In comparison with cells in the control group, HNE1/DDP and C666-1/DDP cells in the si-HOXA11-AS group demonstrated fewer colonies, with an increase in the apoptotic rate, while the expression levels of c-Met, p-Akt/Akt and p-mTOR/mTOR decreased. Moreover, the si-HOXA11-AS-induced enhancement in sensitivity to cisplatin was abolished by miR-454-3p inhibitor transfection. The in vivo experiment showed that DDP in combination with si-HOXA11-AS treatment could inhibit the growth of xenograft tumors. Silencing HOXA11-AS can inhibit the c-Met/AKT/mTOR pathway by specifically upregulating miR-454-3p, thus promoting cell apoptosis and enhancing the sensitivity of cisplatin-resistant NPC cells to cisplatin.
Evidence that population increase and range expansion by Eurasian Sparrowhawks has impacted avian prey populations

The role of increased predator numbers in the general decline of bird populations in the late 20th century remains controversial, particularly in the case of the Eurasian Sparrowhawk, for which there are contradictory results concerning its effect on the abundance of potential prey species. Previous studies of breeding season census data for Sparrowhawks and prey species in Britain have measured predator abundance either as raw presence-absence data or as an estimate derived from spatially explicit modelling, and have found little evidence of association between predator and prey populations. Here, a predator index derived from site-level binary logistic modelling was used in a regression analysis of breeding census data on 42 prey species, with significant effects emerging in 27 species (16 positive, 11 negative). The frequency of significant positive associations may indicate the tracking of prey abundance by Sparrowhawks, which would tend to cancel out any negative predation effect on prey populations, rendering it difficult to detect using census data. If so, the negative effects that have emerged for some species may underestimate the impact of increased Sparrowhawk numbers on the prey populations concerned. Nevertheless, estimates of the effect on national populations of prey species, obtained by combining effect sizes with a measure of the increase in site occupancy by the predator, suggest the possibility of a substantial impact. It cannot, therefore, be ruled out that the increase in abundance and range expansion of Sparrowhawks made a significant contribution to contemporaneous declines in the populations of many of its prey species.
A small proportion of Talin molecules transmit forces to achieve muscle attachment in vivo

Cells in a developing organism are subjected to particular mechanical forces, which shape tissues and instruct cell fate decisions. How these forces are sensed and transmitted at the molecular level is thus an important question, which has mainly been investigated in cultured cells in vitro. Here, we elucidate how mechanical forces are transmitted in an intact organism. We studied Drosophila muscle attachment sites, which experience high mechanical forces during development and require integrin-mediated adhesion for stable attachment to tendons. Hence, we quantified molecular forces across the essential integrin-binding protein Talin, which links integrin to the actin cytoskeleton. Generating flies expressing three FRET-based Talin tension sensors reporting different force levels between 1 and 11 pN enabled us to quantify physiologically-relevant, molecular forces. By measuring primary Drosophila muscle cells, we demonstrate that Drosophila Talin experiences mechanical forces in cell culture that are similar to those previously reported for Talin in mammalian cell lines. However, in vivo force measurements at developing flight muscle attachment sites revealed that average forces across Talin are comparatively low and decrease even further while attachments mature and tissue-level tension increases. Concomitantly, Talin concentration at attachment sites increases five-fold as quantified by fluorescence correlation spectroscopy, suggesting that only few Talin molecules are mechanically engaged at any given time. We therefore propose that high tissue forces are shared amongst a large excess of adhesion molecules of which less than 15% are experiencing detectable forces at the same time. Our findings define an important new concept of how cells can adapt to changes in tissue mechanics to prevent mechanical failure in vivo.
Occurrence of n-Alkanes in Vegetable Oils and Their Analytical Determination

Vegetable oils contain endogenous linear hydrocarbons, namely n-alkanes, ranging from n-C21 to n-C35, with odd chain lengths prevalent. Different vegetable oils, as well as oils of the same type, but of different variety and provenience, show typical n-alkane patterns, which could be used as a fingerprint to characterize them. In the first part of this review, data on the occurrence of n-alkanes in different vegetable oils (total and predominant n-alkanes) are given, with a focus on obtaining information regarding variety and geographical origin. The second part aims to provide the state of the art on available analytical methods for their determination. In particular, a detailed description of the sample preparation protocols and analytical determination is reported, pointing out the main drawbacks of traditional sample preparation and possible solutions to implement the analysis with the aim to shift toward rapid and solvent-sparing methods.
Role of binding immunoglobulin protein (BiP) in Graves' orbitopathy pathogenesis.

Inflammation and adipogenesis represent the main pathogenic mechanisms of Graves' orbitopathy (GO), and oxidative stress is a well-known inducer of GO pathology. Endoplasmic reticulum (ER) stress has been suggested as a major contributor to inflammation and reactive oxygen species (ROS) generation. In this study, we investigated the role of the ER-stress chaperone protein, binding immunoglobulin protein (BiP), in GO pathogenesis. Using primary cultures of orbital fibroblasts from patients with GO, we examined the role of BiP in GO pathogenesis by silencing its expression with small-interfering RNA (siRNA). Inflammatory cytokine expression was analysed by western blotting and enzyme-linked immunosorbent assay. Intracellular ROS levels induced by hydrogen peroxide or cigarette smoke extract were measured by 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. After adipogenic differentiation in BiP siRNA-transfected cells, the cells were stained with Oil Red O, and the levels of adipogenic transcription factors were determined by western blot analysis. BiP mRNA expression levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. Silencing BiP attenuated the expression of pro-inflammatory cytokines (interleukin-6, intercellular adhesion molecule-1, and monocyte chemotactic protein-1) in primary cultured GO orbital fibroblasts. Silencing BiP also reduced ROS generation, hyaluronan production, and adipocyte differentiation. These findings suggest that ER stress is involved in the aetiology of GO and that modulation of ER stress has therapeutic potential for GO.
The Transient Receptor Potential Melastatin 7 (TRPM7) Inhibitors Suppress Seizure-Induced Neuron Death by Inhibiting Zinc Neurotoxicity

Transient receptor potential melastatin 7 (TRPM7) is an ion channel that mediates monovalent cations out of cells, as well as the entry of divalent cations, such as zinc, magnesium, and calcium, into the cell. It has been reported that inhibitors of TRPM7 are neuroprotective in various neurological diseases. Previous studies in our lab suggested that seizure-induced neuronal death may be caused by the excessive release of vesicular zinc and the subsequent accumulation of zinc in the neurons. However, no studies have evaluated the effects of carvacrol and 2-aminoethoxydiphenyl borate (2-APB), both inhibitors of TRPM7, on the accumulation of intracellular zinc in dying neurons following seizure. Here, we investigated the therapeutic efficacy of carvacrol and 2-APB against pilocarpine-induced seizure. Carvacrol (50 mg/kg) was injected once per day for 3 or 7 days after seizure. 2-APB (2 mg/kg) was also injected once per day for 3 days after seizure. We found that inhibitors of TRPM7 reduced seizure-induced TRPM7 overexpression, intracellular zinc accumulation, and reactive oxygen species production. Moreover, there was a suppression of oxidative stress, glial activation, and the blood–brain barrier breakdown. In addition, inhibitors of TRPM7 remarkably decreased apoptotic neuron death following seizure. Taken together, the present study demonstrates that TRPM7-mediated zinc translocation is involved in neuron death after seizure. The present study suggests that inhibitors of TRPM7 may have high therapeutic potential to reduce seizure-induced neuron death.
Developmental acclimation of the thylakoid proteome to light intensity in Arabidopsis

Significance Statement Developmental acclimation to light intensity in plants involves changes in the organisation and regulation of photosynthetic electron transfer chain components in the chloroplast thylakoid membrane. Here, using mass spectrometry, we quantified changes in the thylakoid proteome and correlated these with key photosynthetic parameters to gain insight into the process.
Age, period, and cohort effects on adult mortality due to extrinsic causes of death

This study examines the roles of age, period, and cohort in influenza mortality trends over the years 1959–2016 in the United States. First, we use Lexis surfaces based on Serfling models to highlight influenza mortality patterns as well as to identify lingering effects of early-life exposure to specific influenza virus subtypes (e.g., H1N1, H3N2). Second, we use age-period-cohort (APC) methods to explore APC linear trends and identify changes in the slope of these trends (contrasts). Our analyses reveal a series of breakpoints where the magnitude and direction of birth cohort trends significantly change, mostly corresponding to years in which important antigenic drifts or shifts took place (i.e., 1947, 1957, 1968, and 1978). Whereas child, youth, and adult influenza mortality appear to be influenced by a combination of cohortand period-specific factors, reflecting the interaction between the antigenic experience of the population and the evolution of the influenza virus itself, mortality patterns of the elderly appear to be molded by broader cohort factors. The latter would reflect the processes of physiological capital improvement in successive birth cohorts through secular changes in early-life conditions. Antigenic imprinting, cohort morbidity phenotype, and other mechanisms that can generate the observed cohort effects, including the baby boom, are discussed.
Dual Effect of Soloxolone Methyl on LPS-Induced Inflammation In Vitro and In Vivo

Plant-extracted triterpenoids belong to a class of bioactive compounds with pleotropic functions, including antioxidant, anti-cancer, and anti-inflammatory effects. In this work, we investigated the anti-inflammatory and anti-oxidative activities of a semisynthetic derivative of 18βH-glycyrrhetinic acid (18βH-GA), soloxolone methyl (methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate, or SM) in vitro on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and in vivo in models of acute inflammation: LPS-induced endotoxemia and carrageenan-induced peritonitis. SM used at non-cytotoxic concentrations was found to attenuate the production of reactive oxygen species and nitric oxide (II) and increase the level of reduced glutathione production by LPS-stimulated RAW264.7 cells. Moreover, SM strongly suppressed the phagocytic and migration activity of activated macrophages. These effects were found to be associated with the stimulation of heme oxigenase-1 (HO-1) expression, as well as with the inhibition of nuclear factor-κB (NF-κB) and Akt phosphorylation. Surprisingly, it was found that SM significantly enhanced LPS-induced expression of the pro-inflammatory cytokines interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW264.7 cells via activation of the c-Jun/Toll-like receptor 4 (TLR4) signaling axis. In vivo pre-exposure treatment with SM effectively inhibited the development of carrageenan-induced acute inflammation in the peritoneal cavity, but it did not improve LPS-induced inflammation in the endotoxemia model.