Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer Diagnosis Disclosure and Quality of Life in Elderly Cancer Patients

Informed consent and patient autonomy rights require an optimal cancer diagnosis disclosure strategy to be used to update the patients and caregivers with the bad news. However, a cancer diagnosis disclosure may arouse anxiety and distress which increase patients’ and caregivers’ psychological burden. This study aims to explore the influence of cancer diagnosis disclosure on the quality of life in elderly cancer patients and their caregivers, and to introduce an effective way to disclose cancer diagnosis. A total of 120 participants were randomly selected in the study. The Medical Coping Modes Questionnaire was used to select informed person. The SPIKES was used to guide the disclosure procedures. The informed patients’ or caregivers’ quality of life were evaluated by the Generic Quality of Life Inventory-74 or Caregiver Quality of Life Scale before and after the cancer diagnosis disclosure and at the discharge time. After cancer diagnosis disclosure, no significant change was found on the quality of life of the informed person. With multiple psychological interventions implemented, a significant increase was noticed on the quality of life of the informed person. Applying the cancer diagnosis disclosure strategies and psychological intervention were essential to improve cancer patients’ and caregivers’ quality of life.
Pharmaceutical Preconditioning With Nitric Oxide Synthase and l-Arginine in Ischemic Tissues

Background Nitric oxide (NO) is a multifunctional signaling molecule involved in regulating vascular tone and tissue oxygenation. It is also an important cytoprotective agent against ischemia-reperfusion injury (IRI). Enhancing NO bioavailability via exogenous NO synthases (NOSs) and l-arginine promotes conversation to NO, circumventing the problem of nonfunctioning NOSs under hypoxic and acidic conditions. In this study, the authors evaluated the therapeutic efficacy of neuronal, inducible, and endothelial NOS and l-arginine on reperfusion-induced skin flap alterations. Methods The vascular pedicle isolated rat skin flap model was used and underwent 3 hours of ischemia. At 30 minutes before ischemia, normal saline, endothelial-, inducible-, and neuronal NOSs (1/2 IU) and l-arginine (100 mg/kg body weight) were administered by means of intravenous infusion. The IRI-induced alterations were measured 5 days after the operation. Results The 3 isoforms of NOS increased the flap vitality rate (VR) from 10% to 23% compared with the control group. l-Arginine treatment also increased the VR by approximately 15%. The combination of l-arginine with NOS resulted in even higher flap VRs. The best results could be achieved with the combination of endothelial NOS (2 IU) and l-arginine. Conclusions Modulation of NO bioavailability via exogenous application of NOSs and l-arginine significantly improved VRs in a skin flap rat model. This pharmacologic preconditioning has the potential to attenuate IRI-induced alterations in skin flaps.
The Relationship between Different Types of Alarm Sounds and Children’s Perceived Risk Based on Their Physiological Responses

Due to differences in cognitive ability and physiological development, the evacuation characteristics of children are different from those of adults. This study proposes a novel method of using wearable sensors to collect data (e.g., electrodermal activity, EDA; heart rate variability, HRV) on children’s physiological responses, and to continuously and quantitatively evaluate the effects of different types of alarm sounds during the evacuation of children. In order to determine the optimum alarm for children, an on-site experiment was conducted in a kindergarten to collect physiological data for responses to different types of alarm sounds during the evacuation of 42 children of different ages. The results showed that: (1) The alarm sounds led to changes in physiological indicators of children aged 3–6 years, and the effects of different types of alarm sounds on EDA and HRV activities were significantly different (p < 0.05). Skin conductance (SC), skin conductance tonic (SCT) and skin conductance level (SCL) can be used as the main indicators for analysing EDA of children in this experiment (p < 0.05), and the indicators of ultralow frequency (ULF) and very low frequency (VLF) for HRV were not affected by the type of alarm sounds (p > 0.05). (2) Unlike adults, kindergarten children were more susceptible to the warning siren. The combined voice and warning alarm had optimal effects in stimulating children to perceive risk. (3) For children aged 3–6 years, gender had a significant impact on children’s reception to evacuation sound signals (p < 0.05): Girls are more sensitive than boys in receiving evacuation sound signals, similar to findings of studies of risk perception of adult males and females. In addition, the higher the age, the greater the sensitivity to evacuation sound signals, which accords with results of previous studies on the evacuation dynamics of children.
The mTOR Signaling Pathway Activity and Vitamin D Availability Control the Expression of Most Autism Predisposition Genes

Autism spectrum disorder (ASD) has a strong and complex genetic component with an estimate of more than 1000 genes implicated cataloged in SFARI (Simon′s Foundation Autism Research Initiative) gene database. A significant part of both syndromic and idiopathic autism cases can be attributed to disorders caused by the mechanistic target of rapamycin (mTOR)-dependent translation deregulation. We conducted gene-set analyses and revealed that 606 out of 1053 genes (58%) included in the SFARI Gene database and 179 out of 281 genes (64%) included in the first three categories of the database (“high confidence”, “strong candidate”, and “suggestive evidence”) could be attributed to one of the four groups: 1. FMRP (fragile X mental retardation protein) target genes, 2. mTOR signaling network genes, 3. mTOR-modulated genes, 4. vitamin D3 sensitive genes. The additional gene network analysis revealed 43 new genes and 127 new interactions, so in the whole 222 out of 281 (79%) high scored genes from SFARI Gene database were connected with mTOR signaling activity and/or dependent on vitamin D3 availability directly or indirectly. We hypothesized that genetic and/or environment mTOR hyperactivation, including provocation by vitamin D deficiency, might be a common mechanism controlling the expressivity of most autism predisposition genes and even core symptoms of autism.
Non-Invasive Brain Delivery and Efficacy of BDNF to Stimulate Neuroregeneration and Suppression of Disease Relapse in EAE Mice.

The number of FDA-approved protein drugs (biologics), such as antibodies, antibody-drug conjugates, hormones, and enzymes, continues to grow at a rapid rate; most of these drugs are used to treat diseases of the peripheral body. Unfortunately, most of these biologics cannot be used to treat brain diseases such as Alzheimer's disease (AD), multiple sclerosis (MS), and brain tumors in a non-invasive manner due to their inability to permeate the blood-brain barrier (BBB). Therefore, there is a need to develop an effective method to deliver protein drugs into the brain. Here, we report a proof-of-concept to deliver a recombinant brain-derived neurotrophic factor (BDNF) to the brains of healthy and experimental autoimmune encephalomyelitis (EAE) mice via intravenous (I.V.) injections by co-administering BDNF with a BBB-modulating peptide ADTC5. Western blot evaluations indicated that ADTC5 enhanced the brain delivery of BDNF in healthy SJL/elite mice compared to BDNF alone and triggered the phosphorylation of TrkB receptors in the brain. The EAE mice treated with BDNF+ADTC5 suppressed EAE relapse compared to those treated with BDNF alone, ADTC5 alone or vehicle. We further demonstrated that brain delivery of BDNF induced neuroregeneration via visible activation of oligodendrocytes, remyelination, and ARC & EGR1 mRNA transcript upregulation. In summary, we have demonstrated that ADTC5 peptide modulates the BBB to permit non-invasive delivery of BDNF to exert its neuroregeneration activity in the brains of EAE mice.
Cochlear Implantation with the CI512 and CI532 Precurved Electrode Arrays: One-Year Speech Recognition and Intraoperative Thresholds of Electrically Evoked Compound Action Potentials

Introduction: Precurved cochlear implant (CI) electrode arrays were developed in an attempt to improve the auditory outcome of cochlear implantation, which varies greatly. The recent CI532 (Cochlear Corp., Sydney, Australia) may offer further advantages as its electrode array is thinner than previous precurved CI electrode arrays. The aims here were to investigate 1-year postoperative speech recognition, intraoperative electrically evoked compound action potentials (ECAPs), and their possible relation in patients implanted with a CI532 or its predecessor CI512. Methods: A retrospective analysis of data from 63 patients subjected to cochlear implantation at the Karolinska University Hospital, Sweden, was performed. Speech recognition of the implanted ear was evaluated using phonemically balanced monosyllabic Swedish words at 65 dB SPL. ECAPs were evaluated using the intraoperative ECAP threshold across ≥8 electrodes generated by the automated neural response telemetry of the CI. Results: The median aided speech recognition score (SRS) 1 year after implantation was 52% (quartile 1 = 40%, quartile 3 = 60%, n = 63) and did not differ statistically significantly between patients with CI512 (n = 38) and CI532 (n = 25). The mean ECAP threshold was 188 CL (current level; SD = 15 CL, n = 54) intraoperatively and did not differ statistically significantly between patients with CI512 (n = 32) and CI532 (n = 22), but the threshold for each electrode varied more between patients with a CI512 (p < 0.0001). A higher mean ECAP threshold was associated with a worse SRS (Spearman’s ρ = –0.46, p = 0.0004, n = 54). The association remained among those with a CI512 (Spearman’s ρ = –0.62, p = 0.0001, n = 32) when stratified by CI electrode array. Conclusion: No statistically significant difference in speech recognition 1 year after cochlear implantation or in mean threshold of ECAP intraoperatively was found between patients with a CI512 and the more recent, slim CI532, but the ECAP thresholds varied more between those with a CI512. A statistically significant association between SRS and mean ECAP threshold was found, but stratified analysis suggests that the association may be true only for patients with a CI512.
Noncoding RNAs in inflammation and colorectal cancer

ABSTRACT Despite advanced clinical treatments, mortality in patients with metastatic colorectal cancer (CRC) remains high. Three critical determinants in CRC progression include the epithelial proliferation checkpoints, epithelial‐to‐mesenchymal transition (EMT) and inflammatory cytokines in the tumour microenvironment. Genes involved in these three processes are regulated at the transcriptional and post-transcriptional level. Recent studies revealed previously unappreciated roles of non-coding ribonucleic acids (ncRNAs) in modulating the proliferation checkpoints, EMT, and inflammatory gene expression in CRC. In this review, we will discuss the mechanisms underlying the roles of ncRNAs in CRC as well as examine future perspectives in this field. Better understanding of ncRNA biology will provide novel targets for future therapeutic development.
Methylmercury Induces Metabolic Alterations in Caenorhabditis elegans: Role for C/EBP Transcription Factor.

Methylmercury (MeHg) is a well-known neurotoxicant; however, its role in metabolic diseases has been gaining wider attention. We have previously shown that MeHg causes metabolic alterations in Caenorhabditis elegans (C. elegans), leading to decreased nicotinamide adenine dinucleotide cofactor, mitochondrial dysfunction, and oxidative stress. We were therefore interested in whether MeHg also affects nutrient metabolism, particularly lipid homeostasis, which may contribute to the development of metabolic conditions such as obesity or metabolic syndrome (MS). RNA from wild-type worms exposed to MeHg was collected immediately after treatment, and used for gene expression analysis by DNA microarray. MeHg differentially regulated 215 genes, 17 genes involved in lipid homeostasis, and 12 genes involved in carbohydrate homeostasis. Of particular interest was cebp-1, the worm ortholog to human C/EBP, a pro-adipogenic transcription factor implicated in MS. MeHg increased the expression of cebp-1 as well as pro-adipogenic transcription factors sbp-1 and nhr-49, triglyceride synthesis enzyme acl-6, and lipid transport proteins vit-2 and vit-6. Concurrent with the altered gene expression, MeHg increased triglyceride levels, lipid storage, and feeding behaviors. Worms expressing mutant cebp-1 were protected from MeHg-induced alterations in lipid content, feeding behaviors, and gene expression, highlighting the importance of this transcription factor in the worm's response to MeHg. Taken together, our data demonstrate that MeHg induces biochemical, metabolic, and behavioral changes in C. elegans that can lead to metabolic dysfunction.
Effect of Transcranial Alternating Current Stimulation for the Treatment of Chronic Insomnia: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Clinical Trial

Background: Not all adults with chronic insomnia respond to the recommended therapeutic options of cognitive behavioral therapy and approved hypnotic drugs. Transcranial alternating current stimulation (tACS) may offer a novel potential treatment modality for insomnia. Objectives: This study aimed to examine the efficacy and safety of tACS for treating adult patients with chronic insomnia. Methods: Sixty-two participants with chronic primary insomnia received 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas in the laboratory on weekdays for 4 consecutive weeks, followed by a 4-week follow-up period. The primary outcome was response rate measured by the Pittsburgh Sleep Quality Index (PSQI) at week 8. Secondary outcomes were remission rate, insomnia severity, sleep onset latency (SOL), total sleep time (TST), sleep efficiency, sleep quality, daily disturbances, and adverse events at the end of the 4-week intervention and at the 4-week follow-up. Results: Of 62 randomized patients, 60 completed the trial. During the 4-week intervention, 1 subject per group withdrew due to loss of interest and time restriction, respectively. Based on PSQI, at 4-week follow-up, the active group had a higher response rate compared to the sham group (53.4% [16/30] vs. 16.7% [5/30], p = 0.009), but remission rates were not different between groups. At the end of the 4-week intervention, the active group had higher response and remission rates than the sham group (p < 0.001 and p = 0.026, respectively). During the trial, compared with the sham group, the active group showed a statistically significant decrease in PSQI total score, a shortened SOL, an increased TST, improved sleep efficiency, and improved sleep quality (p < 0.05 or p < 0.001). Post hoc analysis revealed that, in comparison with the sham group, the active group had improved symptoms, except for daily disturbances, at the end of the 4-week intervention, and significant improvements in all symptoms at the 4-week follow-up. No adverse events or serious adverse responses occurred during the study. Conclusion: The findings show that the tACS applied in the present study has potential as an effective and safe intervention for chronic insomnia within 8 weeks.
Identification of Zika Virus NS2B-NS3 Protease Inhibitors by Structure-Based Virtual Screening and Drug Repurposing Approaches

The NS2B-NS3 protease has been identified as an attractive target for drug development against Zika virus (ZIKV) and combined drug repurposing and structure-based virtual screening has improved the development of antiviral drugs. In this study, we performed a structure-based virtual screening of 1861 Food and Administration (FDA) approved drugs available in DrugBank by the selection and docking validation of crystal structure of ZIKV NS2B-NS3 protease (PDB ID 5H4I) using Glide and DOCK 6 software. The antihistaminic chlorcyclizine (Grid score -24.8 Kcal/mol) exhibited the most promising interaction with NS2B-NS3 protease in comparison to crystallography ligand (Grid score -15.6 kcal/mol) by interaction to Tyr161 by hydrophobic interactions in the binding site of NS2B-NS3 which is recognized as an important aminoacid in substrate molecular recognition. Cytotoxicity and global antiviral activity assay in vero cells by MTT method showed that chlorcyclizine reduced the ZIKV induced cytopathic effect (EC50 of 69.0 ± 7.3 µM and SI = 1.9) and explicit molecular dynamics simulations implemented on an NAMD program indicated great stability of chlorcyclizine in protease binding site, suggesting the repurposing of chlorcyclizine as a promising finding in anti-ZIKV drugs development.
Investigation of the Microstructure, Hardness and Corrosion Resistance of a New 58Ag24Pd11Cu2Au2Zn1.5In1.5Sn Dental Alloy

Higher-noble dental alloys (Au, Ag, and Pd) are the most desirable for dentistry applications, but they are expensive. Low-noble (Ag, Pd, Cu) dental alloys are alternatives to higher-noble ones due to their lower price. In this regard, the paper supports the price lowering of dental alloy by increasing the Cu content, i.e., a new 58Ag24Pd11Cu2Au2Zn1.5In1. 5Sn dental alloy. The increasing addition of the Cu leads to a complex structure consisting of a solid solution that engulfs compounds of micrometric and nanometric sizes. The 58Ag24Pd11Cu2Au2Zn1.5In1. 5Sn has demonstrated a much better electrochemical corrosion behavior in artificial saliva compared to the Paliag and Unique White dental alloys. The improved corrosion behavior of the new alloy is supported by the diminishing of the Cu selective diffusion into the electrolyte due to its retaining into compounds and into Ag-Pd solid solution. Also, the synergic effects of Cu, Zn, In, Sn may improve the corrosion resistance, but they have strengthened the 58Ag24Pd11Cu2Au2Zn1.5In1. 5Sn matrix. The main finding addressed in the paper consists in a new 58Ag24Pd11Cu2Au2Zn1.5In1. 5Sn dental alloy with improved corrosion resistance in artificial saliva.
Modelling Vector Transmission and Epidemiology of Co-Infecting Plant Viruses

Co-infection of plant hosts by two or more viruses is common in agricultural crops and natural plant communities. A variety of models have been used to investigate the dynamics of co-infection which track only the disease status of infected and co-infected plants, and which do not explicitly track the density of inoculative vectors. Much less attention has been paid to the role of vector transmission in co-infection, that is, acquisition and inoculation and their synergistic and antagonistic interactions. In this investigation, a general epidemiological model is formulated for one vector species and one plant species with potential co-infection in the host plant by two viruses. The basic reproduction number provides conditions for successful invasion of a single virus. We derive a new invasion threshold which provides conditions for successful invasion of a second virus. These two thresholds highlight some key epidemiological parameters important in vector transmission. To illustrate the flexibility of our model, we examine numerically two special cases of viral invasion. In the first case, one virus species depends on an autonomous virus for its successful transmission and in the second case, both viruses are unable to invade alone but can co-infect the host plant when prevalence is high.
Egg intervention effect on linear growth no longer present after two years

Abstract The Lulun Project, a randomized controlled trial conducted in 2015, found that one egg per day for 6 months during early complementary feeding reduced stunting by 47% and increased linear growth by 0.63 length‐for‐age Z (LAZ). This follow‐up cohort study (Lulun Project II) aimed to test whether the growth effect remained in the egg intervention group compared with the control group after approximately 2 years. Mothers or caregivers from the Lulun Project were recontacted and recruited for this study. Enumerators collected data on socio‐economic and demographic factors, 24‐hr frequency of dietary intakes, morbidities, and anthropometric measures of height, weight, and head circumference using World Health Organization protocols. Statistical analyses followed the same analytical plan as Lulun Project, applying generalized linear models and regression modelling to test group differences in height‐for‐age z (HAZ) from LAZ at Lulun Project endline, and structural equation modelling for mediation. One hundred thirty‐five mother–child dyads were included in Lulun II, with 11% losses to follow‐up from endline Lulun Project. Growth faltering across all children was evident with HAZ −2.07 ± 0.91 and a stunting prevelance of 50%. Regression modelling showed no difference between egg and control groups for the HAZ outcome and other anthropometric outcomes, and significant declines in HAZ from endline Lulun Project in the egg intervention are compared with control groups. Current dietary egg intake, however, was associated with reduced growth faltering in HAZ from Lulun Project endline to Lulun Project II, independent of group assignment and through mediation, explaining 8.8% of the total effect. Findings suggest the need for a longer intervention period and ongoing nutrition support to young children during early childhood.
Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer

Background: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis. Aim: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He. Materials and Methods: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks’ treatment with oral ion and were followed up with complete blood count and iron profile. Results: Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found. Conclusions: We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.