Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemotherapy-generated cell debris stimulates colon carcinoma tumor growth via osteopontin

Colon cancer recurrence after therapy, such as 5‐fluorouracil (5‐FU), remains a challenge in the clinical setting. Chemotherapy reduces tumor burden by inducing cell death; however, the resulting dead tumor cells, or debris, may paradoxically stimulate angiogenesis, inflammation, and tumor growth. Here, we demonstrate that 5‐FU‐generated colon carcinoma debris stimulates the growth of a subthreshold inoculum of living tumor cells in subcutaneous and orthotopic models. Debris triggered the release of osteopontin (OPN) by tumor cells and host macrophages. Both coinjection of debris and systemic treatment with 5‐FU increased plasma OPN levels in tumor‐bearing mice. RNA expression levels of secreted phosphoprotein 1, the gene that encodes OPN, correlate with poor prognosis in patients with colorectal cancer and are elevated in chemotherapy‐treated patients who experience tumor recurrence vs. no recurrence. Pharmacologic and genetic ablation of OPN inhibited debris‐stimulated tumor growth. Systemic treatment with a combination of a neutralizing OPN antibody and 5‐FU dramatically inhibited tumor growth. These results demonstrate a novel mechanism of tumor progression mediated by OPN released in response to chemotherapy‐generated tumor cell debris. Neutralization of debris‐stimulated OPN represents a potential therapeutic strategy to overcome the inherent limitation of cytotoxic therapies as a result of the generation of cell debris. —Chang, J., Bhasin,S. S. , Bielenberg,D. R. , Sukhatme,V. P., Bhasin,M. , Huang,S. , Kieran,M. W. , Panigrahy,D.Chemotherapy‐generated cell debris stimulates colon carcinoma tumor growth via osteopontin. FASEB J. 33,114–125 (2019). www.fasebj. org
Osteoporotic Vertebral Fracture Prevalence Varies Widely

We read with interest articles on osteoporotic vertebral fractures by Oei and colleagues (1) and in the same issue, comparative analysis of radiology of osteoporotic vertebral fractures in women and men by Lentle and colleagues (2). We also note a commentary that follows these two articles by Pawel Szulc (3). Oei and colleagues point out the different methods for radiological assessment of vertebral fractures, but comment on the lack of the gold standard. This article is protected by copyright. All rights reserved.
Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins

Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which results in considerable economic losses. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing the S1 and N proteins and mono-expressing S1 or N proteins of the GX-YL5 strain of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels, as well as the percentages of CD4+ and CD8+ T lymphocytes, were detected within 28 days post-vaccination (dpv). The morbidity, mortality and re-isolation of the virus from the tracheas and kidneys of challenged birds were evaluated at five days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocytes were higher in the rHBM-S1-N vaccinated birds compared to birds vaccinated with the rHBM-S1 and rHBM-N vaccines. At 5 dpc, the mortality, morbidity and virus re-isolation rate of the birds vaccinated with the rHBM-S1-N vaccine were slightly higher than those vaccinated with the H120 control vaccine but were lower than those vaccinated with the rHBM-S1 and rHBM-N vaccines. The present study demonstrated that the protection of the recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing the S1 or N protein. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.
A Hierarchy of Time Scales for Discriminating and Classifying the Temporal Shape of Sound in Three Auditory Cortical Fields

Auditory cortex is essential for mammals, including rodents, to detect temporal “shape” cues in the sound envelope but it remains unclear how different cortical fields may contribute to this ability (Lomber and Malhotra, 2008; Threlkeld et al., 2008). Previously, we found that precise spiking patterns provide a potential neural code for temporal shape cues in the sound envelope in the primary auditory (A1), and ventral auditory field (VAF) and caudal suprarhinal auditory field (cSRAF) of the rat (Lee et al., 2016). Here, we extend these findings and characterize the time course of the temporally precise output of auditory cortical neurons in male rats. A pairwise sound discrimination index and a Naive Bayesian classifier are used to determine how these spiking patterns could provide brain signals for behavioral discrimination and classification of sounds. We find response durations and optimal time constants for discriminating sound envelope shape increase in rank order with: A1 < VAF < cSRAF. Accordingly, sustained spiking is more prominent and results in more robust sound discrimination in non-primary cortex versus A1. Spike-timing patterns classify 10 different sound envelope shape sequences and there is a twofold increase in maximal performance when pooling output across the neuron population indicating a robust distributed neural code in all three cortical fields. Together, these results support the idea that temporally precise spiking patterns from primary and non-primary auditory cortical fields provide the necessary signals for animals to discriminate and classify a large range of temporal shapes in the sound envelope. SIGNIFICANCE STATEMENT Functional hierarchies in the visual cortices support the concept that classification of visual objects requires successive cortical stages of processing including a progressive increase in classical receptive field size. The present study is significant as it supports the idea that a similar progression exists in auditory cortices in the time domain. We demonstrate for the first time that three cortices provide temporal spiking patterns for robust temporal envelope shape discrimination but only the ventral non-primary cortices do so on long time scales. This study raises the possibility that primary and non-primary cortices provide unique temporal spiking patterns and time scales for perception of sound envelope shape.
Depression and medication nonadherence in childhood-onset systemic lupus erythematosus

Objectives Depression and medication nonadherence are important in managing chronic diseases, but little is known about these factors in childhood-onset systemic lupus erythematosus (cSLE). The objectives of this cross-sectional study were to estimate prevalence of depression and medication nonadherence, describe demographic and disease characteristics associated with depression and medication nonadherence, and evaluate the association between depression and medication nonadherence in cSLE patients. Methods Patients with cSLE (n = 51) completed validated screening questionnaires to identify depression and medication nonadherence, Patient Health Questionnaire-9 and Medication Adherence Self-Report Inventory, respectively. Demographic and disease characteristics were obtained via chart abstraction, and compared between groups of depression or medication nonadherence status. A multivariable linear regression model adjusting for propensity scores was conducted to evaluate the association between depression and medication nonadherence. Results The prevalence of a positive depression screen was 58.8%, and seven patients reported suicidal ideation (13.7%). The prevalence of self-reported medication nonadherence was 19.7%. No statistically significant differences for demographic and disease characteristics were found between patients with a positive vs. negative depression screen. Patients reporting medication nonadherence were more likely to have longer disease duration (4.8 vs. 2.6 years, p = 0.035). As the severity of depression symptoms increased, the degree of medication nonadherence also increased (beta = –1.89; p = 0.011). Conclusions The prevalence of depression and medication nonadherence is high in cSLE, and these factors have a direct relationship. Interventions that better recognize and treat depression and increase rates of medication adherence are needed to improve outcomes in cSLE.
The Osteoclast in Bone Metastasis: Player and Target

Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenomenon triggered by tumor cells eventually leading to both tumor proliferation as well as bone deregulation, thus fueling the development of bone metastasis. The complex network, linking tumor cells to the bone by activating osteoclasts, represents a fruitful target for the treatment of bone metastases. In this review we will describe how tumor cells perturb the bone microenvironment by actively influencing osteoclast formation and activity. Moreover, we will describe the current antiresorptive drugs employed in the treatment of bone metastases as well as new, targeted therapies able to affect both cancer cells and osteoclasts.
Valuation of knowledge and ignorance in mesolimbic reward circuitry

Significance Humans desire to know what the future holds. Yet, at times they decide to remain ignorant (e.g., reject medical screenings). These decisions have important societal implications in domains ranging from health to finance. We show how the opportunity to gain information is valued and explain why knowledge is not always preferred. Specifically, the mesolimbic reward circuitry selectively treats the opportunity to gain knowledge about favorable, but not unfavorable, outcomes as a reward to be approached. This coding predicts biased information seeking: Participants choose knowledge about future desirable outcomes more than about undesirable ones, vice versa for ignorance, and are willing to pay for both. This work demonstrates a role for valence in how the human brain values knowledge. The pursuit of knowledge is a basic feature of human nature. However, in domains ranging from health to finance people sometimes choose to remain ignorant. Here, we show that valence is central to the process by which the human brain evaluates the opportunity to gain information, explaining why knowledge may not always be preferred. We reveal that the mesolimbic reward circuitry selectively treats the opportunity to gain knowledge about future favorable outcomes, but not unfavorable outcomes, as if it has positive utility. This neural coding predicts participants’ tendency to choose knowledge about future desirable outcomes more often than undesirable ones, and to choose ignorance about future undesirable outcomes more often than desirable ones. Strikingly, participants are willing to pay both for knowledge and ignorance as a function of the expected valence of knowledge. The orbitofrontal cortex (OFC), however, responds to the opportunity to receive knowledge over ignorance regardless of the valence of the information. Connectivity between the OFC and mesolimbic circuitry could contribute to a general preference for knowledge that is also modulated by valence. Our findings characterize the importance of valence in information seeking and its underlying neural computation. This mechanism could lead to suboptimal behavior, such as when people reject medical screenings or monitor investments more during bull than bear markets.
Antifungal and Cytotoxic Activities of Sixty Commercially-Available Essential Oils

There is an urgent and unmet need for new antifungal therapies. Global fungal infection rates continue to rise and fungal infections pose increasing burdens on global healthcare systems. Exacerbating the situation, the available antifungal therapeutic arsenal is limited and development of new antifungals has been slow. Current antifungals are known for unwanted side effects including nephrotoxicity and hepatotoxicity. Thus, the need for new antifungals and new antifungal targets is urgent and growing. A collection of 60 commercially-available essential oils has been screened for antifungal activity against Aspergillus niger, Candida albicans, and Cryptococcus neoformans, as well as for cytotoxic activity against MCF-7 and MDA-MB-231 human breast tumor cell lines; the chemical compositions of the essential oils have been determined by gas chromatography-mass spectrometry (GC-MS). Ten essential oils showed remarkable antifungal and cytotoxic activities: Indian, Australian, and Hawaiian sandalwoods; melissa; lemongrass; cilantro; cassia; cinnamon; patchouli; and vetiver.
Beyond the reactive‐proactive dichotomy: Rage, revenge, reward, and recreational aggression predict early high school bully and bully/victim status

The role of reactive and proactive aggression in school bullying perpetration remains unclear. In this study, we explore the predictive value of an expanded model of aggression motives based on the Quadripartite Violence Typology (QVT), which distinguishes between motivational valence (appetitive or aversive) and recruitment of deliberative self-control to derive four classes of motives: Rage, Revenge, Reward, and Recreation. With a sample of 1,802 students from grades 7-9, we assessed aggression motives via self-report, along with self-report of bullying perpetration and victimization, which were used to assign students into categories of Pure Bully, Bully/Victim (B/V), Pure Victim, and Uninvolved. Two structural models were computed to examine the relationship between these four categories of bullying involvement and aggression motives, using conservative and liberal bullying cutoffs. As predicted, B/V status was more strongly related to Rage and Revenge motives. However, B/Vs had higher scores than Pure Bullies for almost all aggression motives, including Recreation. We discuss the implications of addressing Revenge and Recreation, as well as Reward and Rage (which map most clearly to proactive and reactive aggression, respectively) aggression motives, for bullying prevention and intervention strategies, especially among adolescents for whom extant bullying prevention strategies may be ineffective or counterproductive.
A novel scoring system for acute myeloid leukemia risk assessment based on the expression levels of six genes

Acute myeloid leukemia (AML) is the most common type of acute leukemia and is a heterogeneous clonal disorder. At present, the pathogenesis of AML and potential methods to effectively prevent AML have become areas of interest in research. In the present study, two messenger ribonucleic acid sequencing datasets of patients with AML were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases. The differentially expressed genes (DEGs) of the poor and good prognosis groups were screened using the Linear Models for Microarray Data package, and the prognosis-related genes were screened using univariate Cox regression analysis. A total of 206 significant DEGs were identified. Following univariate and multivariate Cox regression analysis, 14 genes significantly associated with prognosis were screened and six of these genes, including triggering receptor expressed on myeloid cells 2 (TREML2), cysteine-glutamate transporter (SLC7A11), NACHT, LRR, and PYD domains-containing protein 2 (NLRP2), DNA damage-inducible transcript 4 protein (DDIT4), lymphocyte‑specific protein 1 (LSP1) and C-type lectin domain family 11 member A (CLEC11A), were used to construct model equations for risk assessment. The prognostic scoring system was used to evaluate risk for each patient, and the results showed that patients in the low-risk group had a longer survival time, compared with those in the high-risk group (P=9.59e-06 for the training dataset and P=0.00543 for the validation dataset). A total of eight main Kyoto Encyclopedia of Genes and Genomes pathways were identified, the top three of which were hematopoietic cell lineage, focal adhesion, and regulation of actin cytoskeleton. Taken together, the results showed that the scoring system established in the present study was credible and that the six genes were identified, which were significantly associated with the risk assessment of AML, offer potential as prognostic biomarkers. These findings may provide clues for further clarifying the pathogenesis of AML.
Characteristics Influencing Diversity of Participation of Children in Activities Outside School

OBJECTIVE. A cross‐sectional survey was conducted to determine which personal and environmental characteristics influenced diversity of participation in activities outside school for typically developing children and adolescents. METHOD. Four hundred twenty‐two (215 boys) typically developing Australian children (mean = 11.0 yr) completed the Children's Assessment of Participation and Enjoyment (CAPE) and the Preferences for Activity of Children to describe their participation on five activity types: Recreational, Active Physical, Social, Self‐Improvement, and Skill‐Based. Linear regression analyses were conducted. RESULTS. Predictors of participation diversity were age and preference for Recreational (aR2 = .44); preference for Active Physical (aR2= .19); gender, school type, and preference for Social (aR2 = .19); preference for Skill‐Based (aR2 = .25); and gender, school style, socioeconomic score, and preference for Self‐Improvement (aR2 = .24). CONCLUSION. Preference plays a key role in determining the diversity of participation in activities outside school. &NA; Preference was found to be a key factor in diversity of participation in activities outside school among 422 typically developing Australian children.
Chronic abdominal pain in irritable bowel syndrome – current and future therapies

ABSTRACT Introduction: Irritable bowel syndrome (IBS) is a functional gut disorder that typically manifests in early adult years. One of the two major symptoms of the disease is chronic, visceral pain. The patients report pain as the most distressing symptom with the greatest impact on quality of life, challenging both to patients and healthcare providers. Areas covered: This review focuses on the pathophysiology of abdominal pain in IBS and describes current treatment possibilities. It also covers latest findings that may lead to novel pharmacological options in IBS pain management. Expert commentary: Pain is the main contributor to severity in IBS. Seeking pain alleviation is the most common reason that IBS sufferers consult with their physicians. Not all patients report being satisfied with available treatments for pain in IBS and there is a pressing need to find new, more efficient therapies for this syndrome.
Do patients want to know who accesses their personal health information?: A questionnaire to university students

Personal Health Information (PHI) is collected and used by multiple health professionals and multiple information systems, and usually the patient does not know who accesses their information, when and for what purposes. According to USA (HIPAA) and EU legislation (GDPR) a patient has the right to see his/her clinical information and to know who has access to it, however, the process of obtaining all this related information is still time consuming and complicated. We aim to investigate the opinion of university students regarding the existence of a tool to verify whose healthcare providers access their health information. A web-based questionnaire was designed, 33404 university students were contacted and 589 answered it (1.8% response rate). 90.7% of participants recognize that a tool with those characteristics is important, and 71.5% of them agree to use that tool. In general, we can consider that although the vast majority of participants did not show great knowledge about available healthcare legislation (81%) and that about half of respondents do not know about the use of their data by other parties (52%), more than 90% consider important the existence of a tool to view who accesses their health information. We intend to continue research on this topic and design an access control tool that can empower patients to better control their privacy and rights so to address the gaps existing in the area.
Efficacy of a Hearing Aid Noise Reduction Function

Noise reduction systems have been implemented in hearing aids to improve signal-to-noise ratio and listening comfort. The aim of this study was to evaluate the efficacy of hearing aid noise reduction for Mandarin speakers. The results showed a significant improvement in acceptable noise levels and speech reception thresholds with noise reduction turned on. Sound quality ratings also suggested that most listeners preferred having noise reduction turned on for listening effort, listening comfort, speech clarity, and overall sound quality. These results suggest that the noise reduction system used in this study might improve sentence perception in steady-state noise, noise tolerance, and sound quality, although not all listeners preferred aggressive noise reduction. However, due to large interindividual variation, clinical application of the results should be on an individual basis.
Violent incidents in a secure service for individuals with learning disabilities: Incident types, circumstances and staff responses

BACKGROUND The issue of violence in secure services has long been recognized both in the UK and worldwide. However, there is currently scarce literature available about violence within learning disability (LD) secure settings. METHODS Secondary data analysis was conducted on violent incidents, using information routinely collected by the staff over a 1-year period. RESULTS Physical assaults were the most frequent type of incident, and the distribution in terms of days or months was homogenous and incidents were concentrated in the corridors, lounges and dining rooms of secure facilities. Antipsychotic medication was not regularly prescribed. Generalized linear modelling analyses revealed significant predictors that increased the chances of seclusion and physical restraint, such as being female or directing the violence towards staff. CONCLUSIONS These findings can inform staff training on violence prevention and suggest that increased ward-based supervision and enhanced use of psychological formulations may help in reducing violence within this service context.