Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma

Purpose: The blood–brain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations. Patients and Methods: A first-in-man, single-arm, single-center trial (NCT02253212) was initiated to investigate the transient disruption of the BBB in patients with recurrent GBM. Patients were implanted with a 1-MHz, 11.5-mm diameter cranial ultrasound device (SonoCloud-1, CarThera). The device was activated monthly to transiently disrupt the BBB before intravenous carboplatin chemotherapy. Results: Between 2014 and 2016, 21 patients were registered for the study and implanted with the SonoCloud-1; 19 patients received at least one sonication. In 65 ultrasound sessions, BBB disruption was visible on T1w MRI for 52 sonications. Treatment-related adverse events observed were transient and manageable: a transient edema at H1 and at D15. No carboplatin-related neurotoxicity was observed. Patients with no or poor BBB disruption (n = 8) visible on MRI had a median progression-free survival (PFS) of 2.73 months, and a median overall survival (OS) of 8.64 months. Patients with clear BBB disruption (n = 11) had a median PFS of 4.11 months, and a median OS of 12.94 months. Conclusions: SonoCloud-1 treatments were well tolerated and may increase the effectiveness of systemic drug therapies, such as carboplatin, in the brain without inducing neurotoxicity. See related commentary by Sonabend and Stupp, p. 3750
An Analysis of Pediatric Trauma Center Undertriage in a Mature Trauma System.

BACKGROUND Improved mortality as a result of appropriate triage has been well established in adult trauma and may be generalizable to the pediatric trauma population as well. We sought to determine the overall undertriage rate (UTR) in the pediatric trauma population within Pennsylvania (PA). We hypothesized that a significant portion of pediatric trauma population would be undertriaged. METHODS All pediatric (age <15) admissions meeting trauma criteria (ICD-9: 800-959) from 2003-2015 were extracted from the Pennsylvania Health Care Cost Containment Council (PHC4) database and the Pennsylvania Trauma Systems Foundation (PTSF) registry. Undertriage was defined as patients not admitted to PTSF-verified pediatric trauma centers (n=6). PHC4 contains inpatient admissions within PA while PTSF only reports admissions to PA trauma centers. ArcGIS Desktop was used for geospatial mapping of undertriage. RESULTS 37,607 cases in PTSF and 63,954 cases in PHC4 met criteria, suggesting UTR of 45.8% across PA. Geospatial mapping reveals significant clusters of undertriage regions with high UTR in the eastern half of the state compared to low UTR in the western half. High UTR appears to be centered around non-pediatric facilities. UTR for patients with a probability of death <1% was 39.2%. CONCLUSION Undertriage is clustered in eastern PA with most areas of high undertriage located around existing trauma centers in high density population areas. This pattern may suggest pediatric undertriage is related to a system issue as opposed to inadequate access.Level of evidenceIII.
Stippling of 2D Scalar Fields

We propose a technique to represent two-dimensional data using stipples. While stippling is often regarded as an illustrative method, we argue that it is worth investigating its suitability for the visualization domain. For this purpose, we generalize the Linde–Buzo–Gray stippling algorithm for information visualization purposes to encode continuous and discrete 2D data. Our proposed modifications provide more control over the resulting distribution of stipples for encoding additional information into the representation, such as contours. We show different approaches to depict contours in stipple drawings based on locally adjusting the stipple distribution. Combining stipple-based gradients and contours allows for simultaneous assessment of the overall structure of the data while preserving important local details. We discuss the applicability of our technique using datasets from different domains and conduct observation-validating studies to assess the perception of stippled representations.
New Observations of Meat Eating and Sharing in Wild Bonobos (Pan paniscus) at Iyema, Lomako Forest Reserve, Democratic Republic of the Congo

Bonobos (Pan paniscus) consume a variety of vertebrates, although direct observations remain relatively rare compared to chimpanzees (Pan troglodytes). We report the first direct observations of meat eating and sharing among bonobos at Iyema, Lomako Forest, Democratic Republic of Congo. We collected meat consumption data ad libitum from June to November 2017 over 176.5 observation hours and conducted monthly censuses to measure the abundance of potential prey species. We observed 3 occasions of duiker consumption and found indirect evidence of meat consumption twice (n = 5). We identified the prey species as Weyn’s duiker (Cephalophus weynsi) in all 4 cases that we saw the carcass. This species was the most abundant duiker species at Iyema, but other potential prey species were also available. Meat sharing was observed or inferred during all 3 observations. However, the individual controlling the carcass frequently resisted sharing, and aggressive attempts to take the carcass were observed. This report contributes to a growing body of data suggesting that wild bonobos consume meat at higher rates than previously thought, female control of carcasses is frequent but not exclusive, and meat sharing in bonobos is primarily passive but not without aggression.
UAV Landing Based on the Optical Flow Videonavigation

An automatic landing of an unmanned aerial vehicle (UAV) is a non-trivial task requiring a solution of a variety of technical and computational problems. The most important is the precise determination of altitude, especially at the final stage of approaching to the earth. With current altimeters, the magnitude of measurement errors at the final phase of the descent may be unacceptably high for constructing an algorithm for controlling the landing manoeuvre. Therefore, it is desirable to have an additional sensor, which makes possible to estimate the height above the surface of the runway. It is possible to estimate all linear and angular UAV velocities simultaneously with the help of so-called optical flow (OF), determined by the sequence of images recorded by an onboard camera, however in pixel scale. To transform them into the real metrical values it is necessary to know the current flight altitude and the camera angular position values. The critical feature of the OF is its susceptibility to the camera resolution and the shift rate of the observed scene. During the descent phase of flight, these parameters change at least one hundred times together with the altitude. Therefore, for reliable application of the OF one needs to coordinate the shooting parameters with the current altitude. However, in case of the altimeter fault presence, the altitude is also still to be estimated with the aid of the OF, so one needs to have another tool for the camera control. One of the possible and straightforward ways is the camera resolution change by pixels averaging in computer part which performed in coordination with theoretically estimated and measured OF velocity. The article presents results of such algorithms testing from real video sequences obtained in flights with different approaches to the runway with simultaneous recording of telemetry and video data.
Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts

The skin fibroblast response to reductive stress has been characterized by label-free, data independent acquisition (DIA) proteomics, in the presence or absence of platelet-derived growth factor (PDGF). The fibroblast proteome is remarkably stable in the face of reductive stress, but some key proteins decline, including mitogen activated protein kinase (MAPK) pathway targets and a subset of extracellular matrix proteins. Signal transduction analysis reveals that reductants directly stimulate Akt phosphorylation and modulate MAPK phosphorylation. Graphical Abstract Highlights Changes to the proteome of skin fibroblasts subjected to reductive stress have been quantitated. Only a small set of proteins is selectively diminished upon exposure to reductants. Collagens (COL1A2 and COL6A2) emerge as sentinels of reductive stress. Reductive stress triggers receptor-independent Akt phosphorylation at Ser473. Redox stress is a well-known contributor to aging and diseases in skin. Reductants such as dithiothreitol (DTT) can trigger a stress response by disrupting disulfide bonds. However, the quantitative response of the cellular proteome to reductants has not been explored, particularly in cells such as fibroblasts that produce extracellular matrix proteins. Here, we have used a robust, unbiased, label-free SWATH-MS proteomic approach to quantitate the response of skin fibroblast cells to DTT in the presence or absence of the growth factor PDGF. Of the 4487 proteins identified, only 42 proteins showed a statistically significant change of 2-fold or more with reductive stress. Our proteomics data show that reductive stress results in the loss of a small subset of reductant-sensitive proteins (including the collagens COL1A1/2 and COL3A1, and the myopathy-associated collagens COL6A1/2/3), and the down-regulation of targets downstream of the MAPK pathway. We show that a reducing environment alters signaling through the PDGF-associated MAPK/Akt pathways, inducing chronic dephosphorylation of ERK1/2 at Thr202/Tyr204 and phosphorylation of Akt at Ser473 in a growth factor-independent manner. Our data highlights collagens as sentinel molecules for redox stress downstream of MAPK/Akt, and identifies intervention points to modulate the redox environment to target skin diseases and conditions associated with erroneous matrix deposition.
(Pretty) Lady First: Effects of Mate-Related Motives on the Item-Selection Orders of Faces With Varying Attractiveness

Evolutionary theories suggest that fundamental mating-related motives might exert specific effects on human cognition and behaviors. Based on the evolutionary perspective, our prior research illustrated that the activation of mating-related motives leads to a study-time allocation bias toward highly attractive female faces. While study-time allocation is one of the aspects of the self-regulated learning process, it is unclear whether mating motives affect study decision behaviors (as measured by item-selection orders) during the learning process. Therefore, the present study followed the logic of previous research and aimed to examine the effects of mating-related motives on item-selection orders for face–name associations among faces with varying attractiveness. In two experiments, after an imagery procedure, participants in mating-related priming conditions (Experiment 1: mate search, Experiment 2: mate guarding) or control conditions performed an item-selection task. Participants were shown 16 female faces with varying attractiveness on a computer screen and were instructed to decide the order for studying the faces and corresponding names. Experiment 1 showed that activating mate-search motives led male participants to prioritize the choice of highly attractive rather than less attractive faces for studying. In Experiment 2, compared to the participants in the control condition, female participants in the mate-guarding priming condition were more likely to prioritize the choice of highly attractive rather than less attractive faces for studying. The present findings clarify that mating-related motives affect the item-selection prioritization of faces with varying attractiveness.
Chimeric antigen receptor T-cell therapy: Foundational science and clinical knowledge for pharmacy practice

The Food and Drug Administration has recently approved two autologous chimeric antigen receptor T-cell immunotherapies tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™) for patients with advanced lymphocytic malignancies. Both immunotherapies target the CD19-positive B-cell neoplasms. Kymriah™ is indicated for the treatment of relapsed or refractory acute lymphoblastic leukemia and large B-cell lymphoma. Yescarta™ is indicated for lymphoma only. Although the new therapy offers a promise for patients with advanced disease, it is associated with adverse events including neurotoxicity and cytokine release syndrome, which can be fatal and may require a high level of multidisciplinary supportive care. Due to the risks, both Kymriah™ and Yescarta™ are subject to Risk Evaluation and Mitigation Strategy (REMS) protocols. As active members of multidisciplinary clinical teams, pharmacists are likely to be responsible for the execution of Kymriah™ and Yescarta™ REMS programs. This manuscript describes foundational science and clinical knowledge of chimeric antigen receptor T-cell immunotherapies, common therapy-specific toxicities and REMS requirements for Kymriah™ and Yescarta™ in relation to practice of pharmacy.
[Effect of methanol-ethyl acetate partitioned fractions from Descurainia sophia on proliferation and apoptosis of human non-small cell lung cancer H1975 cells].

OBJECTIVE To investigate the effects of methanol-ethyl acetate partitioned fractions from Descurainia sophia (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells. METHODS The systemic solvent extraction method was used to preliminary separation of the effective fractions in the methanol extract of Descurainia sophia. The cytotoxicity of each extract (5, 10, 20, 40, and 80 μg/mL) was tested using MTT assay. Colony cloning method was used to assess the effect of different concentrations of methanol-ethyl acetate partitioned fractions from MEDS (5, 10, 20, 40, and 80 μg/ mL) on the proliferation of H1975 cells. Flow cytometric analysis with Annexin V-FITC/PI staining was performed to detect the apoptosis of the cells after treatment with different concentrations of MEDS fractions (10, 20, and 40 μg/mL). Western blotting was used to evaluate the effects of MEDS fractions on the expressions of apoptosis-related proteins Akt, Bax, and Bcl-2. The anti-tumor activity of 100 mg/kg MEDS fractions was tested in a nude mouse model bearing H1975 cell xenografts. RESULTS MTT assay and colony forming experiment showed that MEDS fractions significantly inhibited the proliferation of H1975 cells in a dose-and time-dependent manner (P < 0.05). The results of flow cytometry showed that MEDS fractions induced obvious apoptosis of H1975 cells in a concentration-dependent manner (P < 0.05). MEDS fractions also significantly decreased the expressions of Bcl-2 and Akt protein and increased the protein expression of Bax (P < 0.05). In the tumor-bearing nude mouse model, MEDS fractions showed potent anti-tumor effects with a low toxicity to affect the body weight and organs of the mice. CONCLUSIONS The methanol-ethyl acetate partitioned fractions from MEDS show potent anti-tumor activity both in vivo and in vitro, suggesting their value as promising therapeutic agents against lung cancer.
Neuropsychological Function Response to Nocturnal Blue Light Blockage in Individuals With Symptoms of Insomnia: A Pilot Randomized Controlled Study

Abstract Objectives: Insomnia is associated with neuropsychological dysfunction. Evidence points to the role of nocturnal light exposure in disrupted sleep patterns, particularly blue light emitted through smartphones and computers used before bedtime. This study aimed to test whether blocking nocturnal blue light improves neuropsychological function in individuals with insomnia symptoms. Methods: This study used a randomized, placebo-controlled crossover design. Participants were randomly assigned to a 1-week intervention with amber lenses worn in wrap-around frames (to block blue light) or a 1-week intervention with clear lenses (control) and switched conditions after a 4-week washout period. Neuropsychological function was evaluated with tests from the NIH Toolbox Cognition Battery at three time points: (1) baseline (BL), (2) following the amber lenses intervention, and (3) following the clear lenses intervention. Within-subjects general linear models contrasted neuropsychological test performance following the amber lenses and clear lenses conditions with BL performance. Results: Fourteen participants (mean(standard deviation, SD): age = 46.5(11.4)) with symptoms of insomnia completed the protocol. Compared with BL, individuals performed better on the List Sorting Working Memory task after the amber lenses intervention, but similarly after the clear lenses intervention (F = 5.16; p = .014; η2 = 0.301). A similar pattern emerged on the Pattern Comparison Processing Speed test (F = 7.65; p = 0.002; η2 = 0.370). Consideration of intellectual ability indicated that treatment with amber lenses “normalized” performance on each test from approximately 1 SD below expected performance to expected performance. Conclusions: Using a randomized, placebo-controlled crossover design, we demonstrated improvement in processing speed and working memory with a nocturnal blue light blocking intervention among individuals with insomnia symptoms. (JINS, 2019, 25, 668–677)
Cat and Mouse: HIV Transcription in Latency, Immune Evasion and Cure/Remission Strategies

There is broad scientific and societal consensus that finding a cure for HIV infection must be pursued. The major barrier to achieving a cure for HIV/AIDS is the capacity of the HIV virus to avoid both immune surveillance and current antiretroviral therapy (ART) by rapidly establishing latently infected cell populations, termed latent reservoirs. Here, we provide an overview of the rapidly evolving field of HIV cure/remission research, highlighting recent progress and ongoing challenges in the understanding of HIV reservoirs, the role of HIV transcription in latency and immune evasion. We review the major approaches towards a cure that are currently being explored and further argue that small molecules that inhibit HIV transcription, and therefore uncouple HIV gene expression from signals sent by the host immune response, might be a particularly promising approach to attain a cure or remission. We emphasize that a better understanding of the game of “cat and mouse” between the host immune system and the HIV virus is a crucial knowledge gap to be filled in both cure and vaccine research.
The juvenile fibromyalgia syndrome (JFMS): a poorly defined disorder

Juvenile fibromyalgia syndrome (JFMS) is a chronic condition characterized by symptoms of chronic diffuse musculoskeletal pain and multiple painful tender points on palpation. It is often accompanied by fatigue, disorders of sleep, chronic headaches, irritable bowel syndrome, and subjective soft tissue swelling. The complexity of the presenting clinical picture in JPFS has not been sufficiently defined in the literature. Similarities to adult fibromyalgia syndrome in JFMS are often difficult to compare, because many of the symptoms are “medically unexplained” and often overlap frequently with other medical conditions. However, a valid diagnosis of JFMS often decreases parents’ anxiety, reduces unnecessary further investigations, and provides a rational framework for a management plan. The diagnostic criteria proposed by Yunus and Masi in 1985 to define JFMS were never validated or critically analyzed. In most cases, the clinical diagnosis is based on the history, the physical examination that demonstrates general tenderness (muscle, joints, tendons), the absence of other pathological conditions that could explain pain and fatigue, and the normal basic laboratory tests. Research and clinical observations defined that JFMS may have a chronic course that impacts the functional status and the psychosocial development of children and adolescents. This paper briefly reviews the existing knowledge on JFMS focusing on the diagnosis, clinical and the epidemiological characteristics in children and adolescents for better understanding of this disorder. (www.actabiomedica.it)
THE CORRELATION OF NECK CIRCUMFERENCE AND INSULIN RESISTANCE IN NAFLD PATIENTS.

BACKGROUND Insulin resistance, especially that induced by obesity, plays a central role in the development of non-alcoholic fatty liver disease. Although the evaluation of overweight patients is important, the nutritional assessment tools used in clinical practice have limitations. Neck circumference (NC), from this, becomes a viable and low-cost alternative, which seems to be related to the accumulation of fat in the hepatic tissue. OBJECTIVE To evaluate the association between NC and metabolic alterations in patients with non- alcoholic fatty liver disease. METHODS A cross-sectional study performed in 82 patients, of whom 76 underwent liver biopsy. We performed weight, height, abdominal circumference and NC measures. Values of NC ≥42 cm and ≥36 cm were considered as altered for men and women, respectively. Laboratory tests and liver biopsy result were collected in the participants' charts. We evaluated fasting blood glucose levels, insulin, glycosylated hemoglobin, triglycerides, total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ferritin, alkaline phosphatase, gamma glutamyltransferase, albumin, total bilirubin, direct bilirubin, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and the HOMA-IR index. RESULTS We evaluated eighty-two patients. Patients with altered NC had increased body mass index (P=0.043), abdominal circumference (P=0.007), insulin (P=0.003) and HOMA-IR (P=0.029) when compared to those with adequate NC. NC was significantly correlated with reduced levels of high-density cholesterol (HDL-C) in men (r= -042, P<0.05), increased insulin levels in men and female (rs=0.47; P<0.05 and rs=0.51; P<0.01, respectively), as well as higher HOMA-IR index both males (rs=0.49; P<0.01) and female (rs=0.30; P<0.05). There was no significant association between NC and liver outcomes (r=0.145; P=0.36). CONCLUSION NC is associated with the HOMA-IR index in patients with non-alcoholic fatty liver disease. NC can be used in the screening of insulin resistance in these patients, considering that insulin resistance plays a key role in the progression of the disease.