Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Loop-Mediated Isothermal Amplification in a Resource-Saving Strategy for Primary Malaria Screening in a Non-Endemic Setting

Abstract. Malaria is traditionally diagnosed by blood smear microscopy, which requires continuous resource-demanding training. In areas with only a few cases of malaria, a simple and rapid test that can reliably exclude malaria could significantly reduce the need for microscopy and training. We evaluated whether loop-mediated isothermal amplification (LAMP) for screening malaria parasites could reduce the workload in the diagnosis of malaria. Loop-mediated isothermal amplification was used to analyze 38 ethylene-diamine-tetraacetic acid (EDTA) blood samples from 23 patients who had previously been tested for malaria by microscopy, antigen-based rapid diagnostic test (antigen-RDT), and in-house real-time polymerase chain reaction (RT-PCR). The samples included blood with low-level parasitaemia and samples with discrepancies between the results of the different methods. Loop-mediated isothermal amplification detected malaria parasites in 27 of 28 samples that were positive according to in-house RT-PCR. There were negative microscopy results in 10 of these and negative antigen-RDT results in 11. The sample with a negative LAMP result and positive in-house RT-PCR result was from a patient who had recently been treated for low-level Plasmodium falciparum malaria parasitaemia. We found LAMP to be reliable for malaria screening and suitable for replacing microscopy without loss of performance. The low number of LAMP-positive samples needing microscopy can be handled by a limited number of trained microscopists. The time saved on training and documentation was estimated to be 520 working hours yearly in our laboratory. Using LAMP for primary screening of patient samples, we have made a diagnostic workflow that ensures more reliable, faster, and less resource-demanding diagnosis of malaria.
Hepatotoxicity and nephrotoxicity in rats induced by carbon tetrachloride and the protective effects of Teucrium polium and vitamin C

Abstract This work investigated the protective effects of Teucrium polium (T. polium) and vitamin C (Vit C) against carbon tetrachloride (CCl4) induced hepatotoxicity and nephrotoxicity in rats. T. polium reduced the Fer reduced antioxidant power (FRAP) (IC50 = 0.89 mg/ml) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 0.049 µg/ml) than Vit C, FRAP (IC50 = 0.71 mg/ml) and DPPH (IC50 = 0.029 µg/ml). Male albino Wistar rats were divided into six groups: Group I was used as controls, Group II received CCl4 in olive oil (0.5 ml/kg) by gavage, Group III received CCl4 in olive oil (0.5 ml/kg) by gavage after 3 d of receiving T. polium (5 g/l), orally, Group IV received T. polium (5 g/l) alone, by gavage, for 7 d, Group V received CCl4 in olive oil (0.5 ml/kg) by gavage after 3 d of receiving Vit C (250 mg/kg) by gavage and Group VI received Vit C (250 mg/kg) alone by gavage. CCl4 showed an increase of serum hepatic and renal markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. Moreover, we noted an increase of lipid peroxidations and a decrease in antioxidants enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) of CCl4 rats compared to controls. The pretreatment with (200 mg/kg) of T. polium and with Vit C (250 mg/kg) by gavage, for 7 d, displayed their ability to protect against oxidative damage and biochemical changes induced by CCl4. Our results were in accordance with histopathological observations. Graphical Abstract
Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01

An oncolytic adenovirus shows antitumor efficacy in patient-derived models of intraocular retinoblastoma and appears safe for human use. An oncolytic virus to blast retinoblastoma Eyes afflicted by chemoresistant retinoblastoma may need to be surgically removed to prevent life-threatening metastasis. To develop alternative treatments for retinoblastoma, Pascual-Pasto et al. investigated the oncolytic adenovirus VCN-01, which targets cells with dysregulated RB1. They found that VCN-01 can lyse even chemoresistant patient samples in vitro and was effective in mouse xenograft models. VCN-01 was safe in mice and juvenile rabbits. Initial results from the first pediatric retinoblastoma patients treated with intravitreous VCN-01 showed viral replication in tumor cells and no systemic inflammation. These encouraging results support the development of this oncolytic virus to be used for retinoblastoma therapy. Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor RB1. VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity against even chemoresistant retinoblastoma. In vitro, VCN-01 effectively killed patient-derived retinoblastoma models. In mice, intravitreous administration of VCN-01 in retinoblastoma xenografts induced tumor necrosis, improved ocular survival compared with standard-of-care chemotherapy, and prevented micrometastatic dissemination into the brain. In juvenile immunocompetent rabbits, VCN-01 did not replicate in retinas, induced minor local side effects, and only leaked slightly and for a short time into the blood. Initial phase 1 data in patients showed the feasibility of the administration of intravitreous VCN-01 and resulted in antitumor activity in retinoblastoma vitreous seeds and evidence of viral replication markers in tumor cells. The treatment caused local vitreous inflammation but no systemic complications. Thus, oncolytic adenoviruses targeting RB1 might provide a tumor-selective and chemotherapy-independent treatment option for retinoblastoma.
Effectiveness of Simulated Horseback Riding for Patients With Chronic Low Back Pain: A Randomized Controlled Trial.

Context: A simulated horseback riding (SHR) exercise is effective for improvement of pain and functional disability, but its comparative effectiveness with the other is unknown. Objective: The authors aimed to demonstrate the effect of a SHR exercise in people with chronic low back pain. Design: A randomized controlled trial. Settings: Community and university campus. Participants: A total of 48 participants with chronic low back pain were divided into 2 groups, and SHR exercises (n = 24) or stabilization (STB) exercises (n = 24) were performed. Interventions: The exercises were performed for 30 minutes, 2 days per week for 8 weeks. Main Outcome Measures: Numeric rating scale, functional disabilities (Oswestry disability index and Roland-Morris disability), and fear-avoidance beliefs questionnaire (FABQ) scores were measured at baseline and at 4 weeks, 8 weeks, and 6 months. Results: A 2-way repeated analysis of variance identified that between-group comparisons showed significant differences in the FABQ related to work scale (F = 21.422; P = .01). There were no significant differences in the numeric rating scale (F = 1.696; P = .21), Oswestry disability index (F = 1.848; P = .20), Roland-Morris disability (F = 0.069; P = .80), and FABQ related to physical scale (F = 1.579; P = .24). In within-group comparisons, both groups presented significant differences in numeric rating scale (both SHR and STB after 4 wk), Oswestry disability index (both SHR and STB after 6 mo), and Roland-Morris disability (SHR after 6 mo and STB after 8 wk) compared with baseline values. In FABQ-related physical (SHR after 4 wk) and work scales (SHR after 6 mo), there were only significant differences in the SHR compared with baseline values. Conclusions: SHR exercise for 8 weeks had a greater effect than STB exercise for reducing work-related FABQ. The SHR exercise performed in a seated position could substantially decrease pain-related fear disability in young adults with chronic low back pain.
A Parent-Targeted and Mediated Video Intervention to Improve Uptake of Pain Treatment for Infants During Newborn Screening: A Pilot Randomized Controlled Trial

Most newborns undergo newborn screening blood tests. Breastfeeding, skin-to-skin care, and sweet solutions effectively reduce pain; however, these strategies are inconsistently used. We conducted a 2-armed pilot randomized controlled trial in a mother-baby unit to examine the feasibility and acceptability of a parent-targeted and -mediated video demonstrating use of these pain-reducing strategies and to obtain preliminary effectiveness data on uptake of pain management. One hundred parent-newborn dyads were randomized to view the video or receive usual care (51 intervention and 49 control arm). Consent and attrition rates were 70% and 1%, respectively. All participants in the intervention arm received the intervention as planned and reported an intention to recommend the video and to use at least 1 pain treatment with breastfeeding or skin-to-skin care preferred over sucrose. In the intervention arm, 60% of newborns received at least 1 pain treatment compared with 67% in the control arm (absolute difference, −7%; 95% confidence interval, −26 to 12). The video was well accepted and feasible to show to parents. As there was no evidence of effect on the use of pain management, major modifications are required before launching a full-scale trial. Effective means to translate evidence-based pain knowledge is warranted.
Research in haematological cancers: What do patients in the Netherlands prioritise?

Abstract Introduction The experiential knowledge of patients can provide research communities with complementary perspectives on disease. The aim of this study was to identify and prioritise everyday problems and research needs of haematological cancer patients and people who have undergone a stem cell transplantation. Methods A mixed‐method participatory research approach (the Dialogue Model) was applied, including interviews (n = 19), four focus group discussions (n = 27), a questionnaire (n = 146) and a stakeholder dialogue meeting (n = 30) with patients in the Netherlands. Results Patients’ physical discomfort, psychosocial issues, problems with the healthcare system and policy issues were highlighted. Respondents prioritise research aimed at factors potentially influencing survival, such as lifestyle, and research aimed at improving patients’ quality of life, for example improving memory and concentration problems. Topics also focused on physical discomfort, causal mechanisms, and healthcare organisation and policies. Research of a social scientific character is underrepresented, and as such, patients’ everyday problems are not all directly reflected in the research agenda. Conclusions Our findings indicate that patients, besides emphasising the importance of improving survival, have a clear desire to increase control over their lives.
Sprint Assessment Using Machine Learning and a Wearable Accelerometer.

Field-based sprint performance assessments rely on metrics derived from a simple model of sprinting dynamics parameterized by 2 constants, v0 and τ, which indicate a sprinter's maximal theoretical velocity and the time it takes to approach v0, respectively. This study aims to automate sprint assessment by estimating v0 and τ using machine learning and accelerometer data. To this end, photocells recorded 10-m split times of 28 subjects for three 40-m sprints while wearing an accelerometer around the waist. Features extracted from the accelerometer data were used to train a classifier to identify the sprint start and regression models to estimate the sprint model parameters. Estimates of v0, τ, and 30-m sprint time (t30) were compared between the proposed method and a photocell method using root mean square error and Bland-Altman analysis. The root mean square error of the sprint start estimate was . 22 seconds and ranged from . 52 to . 93 m/s for v0, . 14 to . 17 seconds for τ, and . 23 to . 34 seconds for t30. Model-derived sprint performance metrics from most regression models were significantly (P < .01) correlated with t30. Comparison of the proposed method and a physics-based method suggests pursuit of a combined approach because their strengths appear to complement each other.
Immune regulation by glucocorticoids can be linked to cell type–dependent transcriptional responses

Glucocorticoids remain the most widely used immunosuppressive and anti-inflammatory drugs, yet substantial gaps exist in our understanding of glucocorticoid-mediated immunoregulation. To address this, we generated a pathway-level map of the transcriptional effects of glucocorticoids on nine primary human cell types. This analysis revealed that the response to glucocorticoids is highly cell type dependent, in terms of the individual genes and pathways affected, as well as the magnitude and direction of transcriptional regulation. Based on these data and given their importance in autoimmunity, we conducted functional studies with B cells. We found that glucocorticoids impair upstream B cell receptor and Toll-like receptor 7 signaling, reduce transcriptional output from the three immunoglobulin loci, and promote significant up-regulation of the genes encoding the immunomodulatory cytokine IL-10 and the terminal-differentiation factor BLIMP-1. These findings provide new mechanistic understanding of glucocorticoid action and emphasize the multifactorial, cell-specific effects of these drugs, with potential implications for designing more selective immunoregulatory therapies.
Results from e-KISS: electronic-KIOSK Intervention for Safer Sex: A pilot randomized controlled trial of an interactive computer-based intervention for sexual health in adolescents and young adults

Introduction Interactive computer-based interventions (ICBI) are potentially scalable tools for use in real-world settings to promote sexual health and prevent sexually transmitted infections (STIs) and unintended pregnancies. We developed and assessed the feasibility and acceptability of an ICBI for promoting adolescent and young adult sexual health, and the effectiveness of the intervention in reducing unprotected sex, STIs, and unintended pregnancy. Methods This pilot randomized controlled trial enrolled STI Clinic patients, in Seattle, Washington, who were 14–24 years old and reported unprotected vaginal sex during the last 2 months. Both the control and intervention group used a computerized survey to enter their sexual health and only the intervention group received the ICBI. The ICBI included personalized sexual health feedback from a physician avatar; instructive video modules advocating sexual health; and identification of one behavior to change. At 3-month follow-up, participants reported on interim sexual and pregnancy histories and underwent repeat STI testing. We assessed intervention impact on unprotected vaginal sex, number of sexual partners, incident STIs, and unintended pregnancy. Results Of 272 participants, 242 (89%) completed the study, of whom 65% were female. While these findings did not reach statistical significance, at 3-month follow-up, the intervention group reported a 33% lower rate of unprotected vaginal sex (no condom use) [IRR = 0.67, 95% CI: 0.44–1.02]; 29% fewer sex partners [IRR = 0.71, 95% CI: 0.50–1.03]; and 48% fewer STIs [IRR = 0.52, 95% CI: 0.25–1.08] when compared to the control group. Similarly, as compared to the control group, intervention females reported a lower rate of unprotected vaginal sex (no birth control) [IRR = 0.80, 95% CI: 0.47–1.35] and half as many unintended pregnancies (n = 5) versus control females (n = 10) [IRR = 0.51, 95% CI: 0.17–1.58]. In exploratory analyses, intervention females reported fewer partners [IRR = 0.71, 95% CI: 0.50–1.00] and a significantly lower rate of vaginal sex without condoms [IRR = 0.50, 95% CI: 0.30–0.85]. Conclusion The intervention was acceptable to both males and females, and at 3-month follow-up, there were non-significant reductions in risk behavior for all outcomes. Among females, exploratory analysis showed a significant reduction in vaginal sex without condoms.
Coupled Cognitive Changes in Adulthood: A Meta-Analysis

With advancing age, healthy adults typically exhibit decreases in performance across many different cognitive abilities such as memory, processing speed, spatial ability, and abstract reasoning. However, there are marked individual differences in rates of cognitive decline, with some adults declining steeply and others maintaining high levels of functioning. To move toward a comprehensive understanding of cognitive aging, it is critical to know whether individual differences in longitudinal changes interrelate across different cognitive abilities. We identified 89 effect sizes representing shared variance in longitudinal cognitive change from 22 unique datasets composed of more than 30,000 unique individuals, which we meta-analyzed using a series of multilevel metaregression models. An average of 60% of the variation in cognitive changes was shared across cognitive abilities. Shared variation in changes increased with age, from approximately 45% at age 35 years to approximately 70% at age 85 years. There was a moderate-to-strong correspondence (r = .49, congruence coefficient = .98) between the extent to which a variable indicated general intelligence and the extent to which change in that variable indicated a general factor of aging-related change. Shared variation in changes did not differ substantially across cognitive ability domain classifications. In a sensitivity analysis based on studies that carefully controlled for dementia, shared variation in longitudinal cognitive changes remained at upward of 60%, and age-related increases in shared variation in cognitive changes continued to be evident. These results together provide strong evidence for a general factor of cognitive aging that strengthens with advancing adult age.
Nucleus Accumbens Modulation in Reward and Aversion

The nucleus accumbens (NAc) is a key node of the brain’s circuitry that is responsible for translating motivation into action. It has been implicated in playing critical roles in virtually all forms of adaptive and pathological motivated behaviors. It is subject to modulation by a broad array of inputs that influence NAc activity in complex ways that are still poorly understood. Here, we briefly review current knowledge about the behavioral consequences of NAc modulation, focusing on recent studies that use novel techniques developed and implemented over the last decade.
Change in IQ in schizophrenia patients and their siblings: a controlled longitudinal study

Abstract Background Lower intelligence quotient (IQ) has frequently been reported in patients with schizophrenia. However, it is unclear whether IQ declines (further) after illness onset and what the familial contribution is to this change. Therefore, we investigate IQ changes during the course of illness in patients with non-affective psychosis, their siblings and controls. Methods Data are part of the longitudinal Genetic Risk and Outcome of Psychosis (GROUP) study in the Netherlands and Belgium. Participants underwent three measurements, each approximately 3 years apart. A total of 1022 patients with non-affective psychosis [illness duration: 4.34 (s.d. = 4.50) years], 977 of their siblings, and 565 controls had at least one measure of IQ (estimated from four subtests of the WAIS-III). Results At baseline, IQ was significantly lower in patients (IQ = 97.8) and siblings (IQ = 108.2; p < 0.0001) than in controls (IQ = 113.0; p < 0.0001), and in patients as compared with siblings (p < 0.0001). Over time, IQ increased in all groups. In siblings, improvement in IQ was significantly more pronounced (+0.7 points/year) than in patients (+0.5 points/year; p < 0.0001) and controls (+0.3 points/year; p < 0.0001). IQ increase was not significantly correlated with improvement in (sub)clinical outcome in any of the groups. Conclusions During the first 10 years of the illness, IQ increases to a similar (and subtle) extent in a relatively high-functioning group of schizophrenia patients and controls, despite the lower IQ in patients at baseline. In addition, the siblings’ IQ was intermediate at baseline, but over time the increase in IQ was more pronounced.
Tardive dyskinesia is associated with altered putamen Akt/GSK‐3β signaling in nonhuman primates

Tardive dyskinesia is a delayed and potentially irreversible motor complication arising from chronic exposure to antipsychotic drugs. Interaction of antipsychotic drugs with G protein‐coupled receptors triggers multiple intracellular events. Nevertheless, signaling pathways that might be associated with chronic unwanted effects of antipsychotic drugs remain elusive. In this study, we aimed to better understand kinase signaling associated with the expression of tardive dyskinesia in nonhuman primates.
20‐Hydroxy‐ and 20‐carboxy‐leukotriene (LT) B4 downregulate LTB4‐mediated responses of human neutrophils and eosinophils

Leukotriene B4 (LTB4) plays a prominent role in innate immunity as it induces phagocyte recruitment, the release of antimicrobial effectors, and as it potentiates the ingestion and killing of pathogens. In humans, LTB4 has a short half‐life and is rapidly metabolized by leukocytes, notably into 20‐OH‐ and 20‐COOH‐LTB4 by neutrophils. Although these LTB4 metabolites bind to the BLT1 receptor with high affinity, they activate neutrophils to a much lower extent than LTB4. We thus postulated that LTB4 metabolites could dampen BLT1‐mediated responses, therefore limiting the impact of LTB4 on human neutrophil functions. We found that 20‐OH‐LTB4 and 20‐COOH‐LTB4 inhibited all of the LTB4‐mediated neutrophil responses we tested (migration, degranulation, leukotriene biosynthesis). The potencies of the different compounds at inhibiting LTB4‐mediated responses were 20‐OH‐LTB4 = CP 105,696 (BLT1 antagonist) > > 20‐COOH‐LTB4 ≥ resolvin E1 (RVE1). In contrast, the fMLP‐ and IL‐8‐mediated responses we tested were not affected by the LTB4 metabolites or RVE1. 20‐OH‐LTB4 and 20‐COOH‐LTB4 also inhibited the LTB4‐mediated migration of human eosinophils but not that induced by 5‐KETE. Moreover, using 20‐COOH‐LTB4, LTB4, and LTB4‐alkyne, we show that LTB4 is a chemotactic, rather than a chemokinetic factor for both human neutrophils and eosinophils. In conclusion, our data indicate that LTB4 metabolites and RVE1 act as natural inhibitors of LTB4‐mediated responses. Thus, preventing LTB4 ω‐oxidation might result in increased innate immunity and granulocyte functions.