Miracle-dz/UniFAR-FTUs huggingface dataset:
Biologics: A tectonic shift in the management of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints which if ongoing, has a significant bearing in the quality of life and has a variety of systemic manifestation which reduces the overall life span due to an ongoing inflammatory process. There has been a shift in the management of RA right from the early identification of the disease to targeting the pathogenic mechanisms. The changing modalities with emphasis on remission and low disease activity in early RA should be the primary goal. Disease control of RA with the use of combination synthetic disease modifying anti-rheumatic drugs or in combination with biological agents have improved disease-related outcomes. This prevents the progression of disease, morbidity, and has a significant bearing on the overall economic productivity of the patient and the society. Costs of the biological drugs is a major hurdle in their usage. Introduction of biosimilars have lead to a decrease in the cost of the biological molecules and hence their use becoming more widespread. The purpose of this review is to highlight the changing treatment modalities with the advent of biological disease modifiers in RA and a rationale for their use. The strategy in the treatment of RA should be goal directed rather than just relief of symptoms.
Pressing Crowd Noise Impairs the Ability of Anxious Basketball Referees to Discriminate Fouls

The decision-making processes of referees in sports are affected by many factors, including the pressure of spectators. While the home/visitor bias has been previously investigated, the role of crowd noise has been less studied. In the present study, we investigated how the crowd noise (calm vs. pressing) influence the decisions of basketball referees, when examining videos of potential fouls. In doing so, we also considered the level of competitive anxiety of referees (low vs. high anxiety), as factor potentially interacting with the pressure exerted by the spectators. A 2 × 2 ANOVA (Crowd noise x Anxiety) revealed a significant interaction [F(1,28) = 7.33; p < 0.05; ηp2 = 0.21; power = 0.74], with the highly anxious referees showing poorer performances in the pressing crowd condition [t(14) = 2.24; p < 0.05; d = 0.64]. The results indicate that the crowd noise does not seem to affect the referees' decisions, unless we consider the anxiety. The present findings suggest that the decisions of referees with high anxiety might be more easily influenced by external factors like crowd noise. Based on these results, referees' federations should consider the possibility to develop training protocols dedicated to highly anxious referees, to avoid their decisions from being biased by spectators' pressure.
No Differential Reward Responsivity and Drive, Punishment Sensitivity or Attention for Cues Signaling Reward or Punishment in Adolescents With Obesity

Although it has been proposed that obese and healthy weight individuals might differ in their reward and punishment sensitivity, the literature shows diverse and inconsistent findings. The current study was set out to examine the role of reward and punishment sensitivity in adolescent obesity by differentiating between reward responsivity and reward drive, and by complementing self-report measures with performance-based measures indexing attention for cues signaling reward and punishment as well as effort to approach reward and avoid punishment. Participants were adolescents aged 12–23, with obesity (n = 51, adjusted BMI [(actual BMI/Percentile 50 of BMI for age and gender) × 100) between 143 and 313%], and with a healthy weight (n = 51, adjusted BMI between 75 and 129%). Individuals with obesity did not significantly differ from adolescents with a healthy weight in reward responsivity, reward drive or attention to cues signaling reward. Further, no differences in self-reported punishment sensitivity or attention for cues signaling punishment were found between obese and healthy weight adolescents. The current study thus does not corroborate the theories that general reward and punishment sensitivity play a role in obesity.
Gene- and Disease-Based Expansion of the Knowledge on Inborn Errors of Immunity

The recent report of the International Union of Immunological Societies (IUIS) has provided the categorized list of 354 inborn errors of immunity. We performed a systematic analysis of genes and diseases from the IUIS report with the use of the OMIM, ORPHANET, and HPO resources. To measure phenotypic similarity we applied the Jaccard/Tanimoto (J/T) coefficient for HPO terms and top-level categories. Low J/T coefficients for HPO terms for OMIM or ORPHANET disease pairs associated with the same genes indicated high pleiotropy of these genes. Gene ORGANizer enrichment analysis demonstrated that gene sets related to HPO top-level categories were most often enriched in immune, lymphatic, and corresponding body systems (for example, genes from the category “Cardiovascular” were enriched in cardiovascular system). We presented available data on frequent and very frequent clinical signs and symptoms in inborn errors of immunity. With the use of DisGeNET, we generated the list of 25 IUIS/OMIM diseases with two or more relatively high score gene-disease associations, found for unrelated genes and/or for clusters of genes coding for interacting proteins. Our study showed the enrichment of gene sets related to several IUIS categories with neoplastic and autoimmune diseases from the GWAS Catalog and reported individual genes with phenotypic overlap between inborn errors of immunity and GWAS diseases/traits. We concluded that genetic background may play a role in phenotypic diversity of inborn errors of immunity.
Eupafolin Suppresses Esophagus Cancer Growth by Targeting T-LAK Cell-Originated Protein Kinase

Eupafolin is the main bioactive component extracted from the traditional Chinese medicine Ay Tsao (Artemisia vulgaris L.), and its anti-tumor activity has had been studied in previous researches. T-LAK cell-originated protein kinase (TOPK) belongs to serine/threonine protein kinase and is highly expressed in several cancer cells and tissues, such as colon cancer, lung cancer, esophagus cancer, and so on. Therefore, it was recognized as an important target for treating tumors. Nowadays, we found that eupafolin suppressed TOPK activities at the first time in vitro and in vivo. The cells study indicated that eupafolin suppressed TOPK activities in JB6 Cl41 and KYSE450 cells. Furthermore, knockdown of TOPK in KYSE450 cells decreased their sensitivities to eupafolin. The animal study showed that the injection of eupafolin in patient-derived xenograft (PDX) mouse effectively suppressed tumor growth. Histone H3 and Ki67 were reduced, and cleaved caspase 3 was increased in tumor tissues after eupafolin treatment. To sum up, eupafolin as an TOPK inhibitor can suppress growth of esophagus cancer in vitro and in vivo. The TOPK downstream signaling molecule histone H3 in tumor tissues was also reduced after eupafolin treatment. In short, eupafolin can suppress growth of esophagus cancer cells as an TOPK inhibitor both in vitro and in vivo.
Children’s Academic, Artistic, and Athletic Competencies: Successes Are in the Eye of the Beholder

A significant challenge to fully understanding children’s academic and other competencies is dependency of the determination on the method of study, including notably who makes the assessment. This study examined similarities and differences in child, mother, father, and teacher reports of children’s competencies across multiple domains of math, reading, music, and sports from two separate perspectives of rater agreement, mean level and order association. Two hundred and sixty-seven European American families were recruited from the mid-Atlantic region of the United States, and children, mothers and fathers, and teachers completed a commonly used rating measure of children’s competencies when the children were 10 years of age. Results showed (1) high levels of order agreement (perhaps reflecting the observable nature of children’s competencies), (2) some systematic mean level differences across raters, and (3) little inter-domain agreement (except among teachers, which may reflect teachers’ unique perspectives on children’s competencies). The educational, developmental, and methodological implications of the findings are discussed in the context of children’s school performance. Who makes the determination of children’s several different competencies matters.
Food-Specific Inhibitory Control Mediates the Effect of Disgust Sensitivity on Body Mass Index

Disgust is an emotion that drives food avoidance. People vary in their responses to disgust, which is captured by their disgust sensitivity. Disgust sensitivity is clinically significant because it can influence eating behaviors, and indirectly people’s body mass index (BMI). Inhibitory control can also influence BMI through the role that such reflective abilities play in governing food intake. In this study, we relied on neural models of disgust to suggest that disgust and inhibitory control are intertwined, and that inhibitory control facilitates the translation of disgust sensitivity into BMI. Mediation analyses applied to 46 subjects, including 29 normal body weight [BMI = 18.34 kg/m2 (SD = 1.58)] and 17 overweight/obese [BMI = 26.03 kg/m2 (SD = 2.58)] subjects, were used to test the hypothesis. Subjects completed the Chinese version of the Disgust Scale-Revised, and an inhibition control test (Food-Specific Stop-Signal Task). There were negative correlations between the disgust sensitivity score (DS) and body mass index (BMI), and between DS and stop-signal reaction time (SSRT). Moreover, BMI was positively correlated with SSRT. The mediation model results showed that disgust sensitivity was associated with BMI and that this relationship was mediated via inhibition control. There was no significant effect of DS on BMI, while the effect of SSRT on BMI was significant. This suggested that the effect of disgust sensitivity on BMI was fully mediated through food-specific inhibitory control. This supports our hypothesis that BMI is affected by disgust sensitivity and that this relationship is mediated by inhibition control. These findings reveal a key mechanism that underlies disgust sensitivity-BMI association and point to future research and potential interventions aimed at food intake management.
Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer

Despite decades of research and major efforts, malignant brain tumors remain among the deadliest of all cancers. Recently, an increasing number of psychiatric drugs has been proven to possess suppressing activities against brain tumors, and rapid progress has been made in understanding the potential mechanisms of action of these drugs. In particular, the traditional mood stabilizer valproic acid, the widely used antidepressants fluoxetine and escitalopram oxalate, and the atypical psychiatric drug aripiprazole have demonstrated promise for application in brain tumor treatment strategies through multiple lines of laboratory, preclinical, and clinical evidence. The unexpected discovery of the anticancer properties of these drugs has ignited interest in the repurposing of other psychiatric drugs to combat brain cancer. In this review, we synthesize recent progress in understanding the potential molecular mechanisms underlying the brain cancer–killing activities of representative psychiatric drugs. We also identify key limitations in the repurposing of these medications that must be overcome to enhance our ability to successfully prevent and treat brain cancer, especially in the most vulnerable groups of patients, such as children and adolescents, pregnant women, and those with unfavorable genetic variants. Moreover, we propose perspectives that may guide future research and provide long-awaited new hope to patients with brain cancer and their families.
Epstein-Barr Virus BART Long Non-coding RNAs Function as Epigenetic Modulators in Nasopharyngeal Carcinoma

Epstein-Barr virus (EBV) establishes lifelong latent infection in humans and is associated with several lymphoid and epithelial cancers. In nasopharyngeal carcinoma (NPC), EBV expresses few viral proteins but elevated levels of Bam-HI A rightward transcripts (BARTs) RNA, which includes viral microRNAs and long non-coding RNAs (lncRNAs). BART lncRNAs localize within the nucleus of EBV-infected cells and knockdown of BART lncRNAs significantly affects the expression of genes associated with cell adhesion, oxidoreductase activity, inflammation, and immunity. Notably, downregulation of IKAROS family zinc finger 3 (IKZF3/Aiolos), which plays a role in lymphocyte development and cell attachment, occurred in NPC C666-1 cells following BART lncRNA-knockdown. Since Aiolos expression is normally restricted to lymphoid cells and rarely observed in epithelial cells, induction of Aiolos by BART lncRNA was confirmed by expressing the major BART lncRNA isoform, RPMS1, in EBV-positive and -negative cells. BART lncRNA associated with the CBP/p300 complex and RNA polymerase II (Pol II) in the nucleus, suggesting that BART lncRNAs may mediate epigenetic regulation of gene expression through interaction with the chromatin remodeling machinery. This contention is further supported by evidence that BART lncRNA appears to stall Pol II at the promoter region and may regulate IFNB1 and CXCL8 expression by inhibiting transcription by Pol II in NPC. We hypothesize that EBV BART lncRNA expression modulates host gene expression and maintains EBV latency by interfering with histone methylation and acetylation processes. Aberrant expression of affected host genes mediated by BART lncRNA may lead to immune evasion, progression, and metastasis of NPC.
Effect of Meditative Movement on Affect and Flow in Qigong Practitioners

Qigong is a Meditative Movement exercise that consists of mindful movements, regulation of breathing and attentional control. In this study we investigated whether Qigong practice might be associated with the affect and flow of its practitioners during the exercise. Although practitioners of Meditative Movement anecdotally describe flow-like experiences and strong effects on affect there are only a few empirical studies that focus on acute effects of Qigong practice on affect, and to our knowledge none on flow. Understanding these phenomena could shed new light on the interrelationship between body movement and the embodied mind. Self-reported affect and flow of qigong practitioners (N = 19) was probed in four qigong sessions, 1 week apart, each lasting about an hour. We used the PANAS (Positive And Negative Affect Schedule) to measure self-reported affect pre- and post-session. Additionally, open-ended questions were used to further inquire the specific quality of the post-session affect. Flow was measured using the Flow Short Scale, twice during each Qigong session and once after it. Our results confirm previous studies that Qigong practice shifts affect toward positive valence. Content analysis of the open-ended questions further revealed that the resulting experience can be described as restful, relaxed, happy, balanced, and clear. Although the lack of a control group/condition preclude drawing firm causal conclusions, our results indicate that Qigong practice produced flow already 20 min into the session, and that flow state intensified at 40 and 60 min. Future directions for studying affect and flow in meditative exercise are discussed.
Screening and Initiating Supportive Care in Patients With Heart Failure

Background: Patients with heart failure (HF) experience a major symptom burden and an overall reduction of quality of life. However, supportive care (SC) remains an under-utilized resource for these patients. Among the many existing barriers to integrating SC into routine care, identifying patients with SC needs remains challenging. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is an important predictor of SC needs in patients with HF. Methods and Results: We used the shortened version KCCQ-12 as a screening tool for SC need in our ambulatory HF patient population using a KCCQ-12 summary score of <29 as the cut-off. Of the 456 patients who completed the KCCQ-12, 41 (9%) were predicted to have SC needs. Demographics, medical history, biochemical parameters, echocardiographic assessment and medical treatment were similar between the two groups of patients. However, patients with KCCQ-12 <29 were more symptomatic based on both New York Heart Association (NYHA) classification and American Heart Association (AHA) staging with a higher prevalence of depression. We established a multidisciplinary SC clinic and the profile and outcomes of patients with SC needs that were referred and followed at our SC clinic were also evaluated. Twenty-three patients were referred to our SC clinic: 2 died before being seen, 1 refused SC and 20 received SC. Of these 20 patients, 11 died and 9 are currently being followed. Median survival after starting the SC clinic is 3 months. In the original SC cohort of 23, 17 patients had available KCCQ-12 summary scores. However, only 6 out of 17 (35%) had KCCQ-12 scores <29, indicating the need for additional assessment tools in this patient population. Conclusions: The magnitude of unmet supportive care needs in patients with HF is significant. While the KCCQ-12 questionnaire is a useful tool to identify patients with SC, serial clinical evaluation, establishment of a SC clinic and prompt referral are essential for patients needing supportive care.
Lithraea caustic (Litre) Extract Promotes an Antitumor Response Against B16 Melanoma

Melanoma immunotherapy, specifically the autotransplant of dendritic cells charged with tumors antigens, has shown promising results in clinical trials. The positive clinical effects of this therapy have been associated to increased Th17 response and delayed-type hypersensitivity (DTH) against to tumor antigens. Some synthetic compounds, such as diphenylcyclopropenone (DPCP), are capable of triggering a DTH response in cutaneous malignancies and also to induce clinically relevant effects against melanoma. In this work, we evaluated Litre extract (LExT), a standardized extract of a Chilean stinging plant, Lithraea caustic (Litre). As Litre plant is known to induce DTH, we used a murine B16 melanoma model to compare the topical and intratumor efficacy of LExT with synthetic DTH inducers (DPCP and 2,4-dinitrochlorobenzene [DNCB]). LExt contained mainly long chain catechols and sesquiterpenes. The intratumor injection of LExT induced a significant delay in tumor growth, similarly topical treatment of an established tumor with 0.1% LExT ointment induced a growth delay and even tumor regression in 15% of treated animals. No significant changes were observed on the T-cell populations associated to LExT treatment, and neither DNCB nor DPCP were capable to induce none of the LExT-induced antitumoral effects. Interestingly, our results indicate that LExT induces an antitumor response against melanoma in a mouse model and could bring a new –and affordable- treatment for melanoma in humans.
Recent Advances in Nanomaterials-Based Chemo-Photothermal Combination Therapy for Improving Cancer Treatment

Conventional chemotherapy for cancer treatment is usually compromised by shortcomings such as insufficient therapeutic outcome and undesired side effects. The past decade has witnessed the rapid development of combination therapy by integrating chemotherapy with hyperthermia for enhanced therapeutic efficacy. Near-infrared (NIR) light-mediated photothermal therapy, which has advantages such as great capacity of heat ablation and minimally invasive manner, has emerged as a powerful approach for cancer treatment. A variety of nanomaterials absorbing NIR light to generate heat have been developed to simultaneously act as carriers for chemotherapeutic drugs, contributing as heat trigger for drug release and/or inducing hyperthermia for synergistic effects. This review aims to summarize the recent development of advanced nanomaterials in chemo-photothermal combination therapy, including metal-, carbon-based nanomaterials and particularly organic nanomaterials. The potential challenges and perspectives for the future development of nanomaterials-based chemo-photothermal therapy were also discussed.
Declines and Resilience of Communities of Leaf Chewing Insects on Missouri Oaks Following Spring Frost and Summer Drought

Extreme weather events dramatically impact populations of individual insect species but the consequences of such events for entire insect communities are not well documented. We present evidence that late spring frosts and summer drought negatively affect the community of insects found on Missouri oaks (Quercus alba and Q. velutina), amounting to a 23-186 fold decrease depending on the oak species, insect size and feeding guild, and the specific weather event. Spring faunas required three years or more following spring frosts to reach pre-event levels, whereas summer faunas were more resilient, rebounding within 1-2 years. The impact of summer drought on leaf tying caterpillars, however, lasted longer than that of the spring frost; it was five years before numbers of leaf ties reached pre-drought levels. Smaller species of leaf tying Lepidoptera took longer to recover than larger species following the drought. Overall, we found no evidence for a general decline in abundance, even a modest one, during the 20 years of study of faunas on oak trees in southeastern Missouri. However, the effects of drought reported here are likely to increase with time as the climate in the Midwest U.S. is only expected to become warmer and drier during the summer months. Similarly, the risk of late season frost damage to trees is expected to increase with predicted earlier onset of spring. Understanding the impact of such weather events on insect communities influences our ability to predict how habitat and landscape management, or lack thereof, will influence future patterns of insect abundance and diversity.
Sub-millisecond Control of Neuronal Firing by Organic Light-Emitting Diodes

Optogenetics combines optics and genetics to enable minimally invasive cell-type-specific stimulation in living tissue. For the purposes of bio-implantation, there is a need to develop soft, flexible, transparent and highly biocompatible light sources. Organic semiconducting materials have key advantages over their inorganic counterparts, including low Young's moduli, high strain resistances, and wide color tunability. However, until now it has been unclear whether organic light emitting diodes (OLEDs) are capable of providing sufficient optical power for successful neuronal stimulation, while still remaining within a biologically acceptable temperature range. Here we investigate the use of blue polyfluorene- and orange poly(p-phenylenevinylene)-based OLEDs as stimuli for blue-light-activated Sustained Step Function Opsin (SFFO) and red-light-activated ChrimsonR opsin, respectively. We show that, when biased using high frequency (multi-kHz) drive schemes, the OLEDs permit safe and controlled photostimulation of opsin-expressing neurons and were able to control neuronal firing with high temporal-resolution at operating temperatures lower than previously demonstrated.