Miracle-dz/UniFAR-FTUs huggingface dataset:
The Injury Response to DNA Damage Promotes Anti-Tumor Immunity

Inhibition of immune checkpoints has shown promising results in the treatment of certain tumor types. However, the majority of cancers do not respond to immune checkpoint inhibition (ICI) treatment, indicating the need to identify additional modalities that enhance the response to immune checkpoint blockade. In this study, we identified a tumor-tailored approach using ex-vivo DNA damaging chemotherapy-treated tumor cells as a live injured cell adjuvant. Using an optimized ex vivo system for dendritic cell-mediated T-cell IFN-γ induction in response to DNA-damaged tumor cells, we identified specific dose-dependent treatments with etoposide and mitoxantrone that markedly enhance IFN-γ production by T-cells. Unexpectedly, the immune-enhancing effects of DNA damage failed to correlate with known markers of immunogenic cell death or with the extent of apoptosis or necroptosis. Furthermore, dead tumor cells alone were not sufficient to promote DC cross-presentation and induce IFN-γ in T-cells. Instead, the enhanced immunogenicity resided in the fraction of injured cells that remained alive, and required signaling through the RIPK1, NF-kB and p38MAPK pathways. Direct in vivo translation of these findings was accomplished by intra-tumoral injection of ex vivo etoposide-treated tumor cells as an injured cell adjuvant, in combination with systemic anti-PD1/CTLA4 antibodies. This resulted in increased intra-tumoral CD103+ dendritic cells and circulating tumor antigen-specific CD8+ T-cells, leading to enhanced anti-tumor immune responses and improved survival. The effect was abrogated in BATF3-deficient mice indicating that BATF3+ DCs are required for appropriate T-cell stimulation by live but injured DNA-damaged tumor cells. Notably, injection of the free DNA-damaging drug directly into the tumor failed to elicit such an enhanced anti-tumor response as a consequence of simultaneous damage to dendritic cells and T-cells. Finally, the DNA damage induced injured cell adjuvant and systemic ICI combination, but not ICI alone, induced complete tumor regression in a subset of mice who were then able to reject tumor re-challenge, indicating induction of a long-lasting anti-tumor immunological memory by the injured cell adjuvant treatment in vivo.
Leveraging UMLS-driven NLP to enhance identification of influenza predictors derived from electronic medical record data

Objective Multiple clinical prediction rules have been developed, but lack validation. This study aims to identify a set of prediction algorithms for influenza, based on electronic health record (EHR) structured data and clinical notes derived data using Unified Medical Language System (UMLS) driven natural language processing (NLP). Materials and Methods Data were extracted from an enterprise-wide data warehouse for all patients who tested positive for influenza and were seen in ambulatory care between 2009 and 2019 (N = 7,278). A text processing pipeline was used to analyze chart notes for UMLS terms for symptoms of interest to improve data quality completeness. Three models, which step up complexity of the dataset and predictors, were tested with least absolute shrinkage and selection operator (LASSO)-selected parameters to identify predictors for influenza. Receiver operating characteristic (ROC) curves compared test accuracy across the three models. Results Three models identified 7, 8, and 10 predictors, and the most complex model performed best. The addition of the UMLS-driven NLP symptoms data improved data quality (false negatives) and increased the number of significant predictors. NLP also increased the strength of the models, as did the addition of two-way predictor interactions. Discussion The EHR is a feasible source for offering rapidly accessible datasets for influenza related prediction research that was used to produce a prediction model for influenza. Combining data collected in routine care with data science methods improved a prediction model for influenza, and in the future, could be used to drive diagnostics at the point of care.
Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies

ABSTRACT Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined.
Targeted CRM1-inhibition perturbs leukemogenic NUP214 fusion proteins and exerts anti-cancer effects in leukemia cell lines with NUP214 rearrangements

Chromosomal translocations fusing the locus of nucleoporin NUP214 each with the proto-oncogenes SET and DEK are recurrent in, largely intractable, acute leukemias. The molecular basis underlying the pathogenesis of SET-NUP214 and DEK-NUP214 are still poorly understood, but both chimeras inhibit protein nuclear export mediated by the ß-karyopherin CRM1. In this report, we show that SET-NUP214 and DEK-NUP214 both disturb the localization of proteins essential for nucleocytoplasmic transport, in particular for CRM1-mediated protein export. Endogenous and exogenous SET-NUP214 and DEK-NUP214 form nuclear bodies. These nuclear bodies disperse upon targeted inhibition of CRM1 and the two fusion proteins re-localize throughout the nucleoplasm. Moreover, SET-NUP214 and DEK-NUP214 nuclear bodies reestablish shortly after removal of CRM1 inhibitors. Likewise, cell viability, metabolism, and proliferation of leukemia cell lines harboring SET-NUP214 and DEK-NUP214 are compromised by CRM1 inhibition, which is even sustained after clearance from CRM1 antagonists. Our results indicate CRM1 as a possible therapeutic target in NUP214-related leukemia. This is especially important, since no specific or targeted treatment options for NUP214 driven leukemia are available yet.
Investigation of the effect of L-Carnitine on Mouse Ovarian Transplantation

Introduction: L-carnitine (LC) has yielded relevant results on ischaemic/ reperfusion (I/R) injuries in organs such as the intestine, liver, kidney, brain and heart, because of its antioxidant activity. We aimed to evaluate the potential of using L-carnitine to improve the quality of grafted ovarian tissues. Materials and methods: The ovaries from 4-6-week old mice were grafted into back muscle site. Transplanted ovaries were divided into four groups. 200 mg/kg LC was injected intraperitoneally one day before surgical operation RESEARCH 24(101), January February, 2020 Medical Science ISSN 2321–7359 EISSN 2321–7367
Evaluation of Diachasmimorpha longicaudata (Hymenoptera: Braconidae) as a mortality factor of Ceratitis capitata (Diptera: Tephritidae) infesting Citrus species under laboratory and field-cage conditions

Abstract Ceratitis capitata (or medfly) is one of the major pests currently affecting fruit crops in northwestern Argentinian Citrus-producing areas. Medfly populations are sustained in large exotic fruits, such as Citrus paradisi, Citrus aurantium and Citrus sinensis, which are known to hinder the activity of almost all native parasitoid species. Therefore, a feasible approach to controlling medfly involves the use of exotic parasitoids such as Diachasmimorpha longicaudata. In this study, the prediction that parasitoid females would be proficient at finding medfly larvae infesting the Citrus species mentioned earlier was tested. Particularly, the variation in fruit species preference by parasitoid females, the efficacy of the parasitoid to kill medfly and the effect of host density on parasitoid performance were determined. Parasitoids were allowed to forage for 8 h on grapefruits and oranges artificially infested with medfly larvae under controlled (laboratory) and uncontrolled (field cage) environmental conditions. Fruit choice and no-choice tests were performed. Results were assessed by comparing the number of female visits to and ovipositor insertions into the fruit, and parasitoid emergence, parasitism and additional host mortality percentages. Parasitoid preference for visiting larger fruits (sour orange and grapefruit) may be related to the increased fruit surface area. Ovipositional activity on fruit was influenced by the variation of the larval host density per unit of fruit surface. The higher parasitism rates recorded from sweet orange would be mainly a result of both increased host density and fruit physical features. Nevertheless, D. longicaudata showed the capacity to parasitise hosts in all Citrus species tested.
Phylogeny of the Sympetrinae (Odonata: Libellulidae): further evidence of the homoplasious nature of wing venation

Abstract Sympetrinae is the largest subfamily of the diverse dragonfly family Libellulidae. This subfamily, like most libellulid subfamilies, is defined currently by a few wing venation characters, none of which are synapomorphies for the taxon. In this study, we used DNA sequence data from the nuclear locus elongation factor‐1α and the mitochondrial loci 16S and 12S rRNA, together with 38 wing venation characters, to test the monophyly of the Sympetrinae and several other libellulid subfamilies. No analysis recovered Sympetrinae as monophyletic, partly because of the position of Leucorrhinia (of the subfamily Leucorrhininae) as a strongly supported sister to Sympetrum (of Sympetrinae) in all analyses. The subfamilies Brachydiplactinae, Leucorrhininae, Trameinae and Trithemistinae were also found not to be monophyletic. Libellulinae was the only subfamily supported strongly as monophyletic. Consistency indices and retention indices of wing venation characters used to define various subfamilies were closer to zero than unity, showing that many of these characters were homoplasious, and therefore not useful for a classification scheme within Libellulidae.
Novel strategies for enhancing tissue integration in cartilage repair

Introduction Articular cartilage is unable to initiate a spontaneous repair response when injured due to its avascular and aneural properties. Within adult cartilage, chondrocytes are entrapped within an extensive extracellular matrix and are unable to migrate to sights of injury to regulate tissue repair. Injury to this tissue therefore inevitably leads to degeneration of the cartilage and the development of degenerative diseases such as osteoarthritis.
Mating disruption for the control of the olive moth, Prays oleae (Bern) (Lep., Yponomeutidae) with the ajor sex pheromone component

Abstract: Mating disruption to control the olive moth Prays oleae (Bern) was tested from 1992 to 1996 in olive groves in Greece. The major sex pheromone component (Z)‐7‐tetradecenal was formulated in β‐cyclodextrin (β‐CD) and polyvinyl chloride (PVC) polymers. Pheromone trap catches were reduced by up to 96–100% in the mating‐disruption plots. During the first year of mating disruption a treatment with Bacillus thuringiensis (var. kurstaki) (Bt) was applied to reduce the first generation or larvae. Fruit damage in the mating disruption plots was lower compared with the fruit damage in Bt, insecticide and untreated plots. In high fruiting years, the proportion of fruit damage was lower than in low fruiting years. Mating disruption applied in the same olive grove over several years progressively reduced the olive moth population from year to year.
Meiotic Studies in Some Species of Pennisetum Pers. (Poaceae) from the Western Himalayas

At present, cytological studies have been carried out on a population basis for assessing the genetic diversity in seven species of the genus Pennisetum, P. alopecuroides (n = 18), P. americanum (n = 7), P. flaccidum (n = 27), P. lanatum (n = 18, 21), P. orientale (n = 18), P. purpureum (n = 14, 18, 21) and P. ramosum (n = 5), from phytogeographically different areas of Himachal Pradesh and Kashmir in the Western Himalayas. For P. lanatum and P. purpureum, the chromosomal counts of n = 21 make first ever records of new cytotypes on a worldwide basis. In addition, P. lanatum and P. purpureum with n = 18 make new records in India. Both the cytotypes of P. lanatum and three different cytotypes of P. purpureum show some marked differences in their morphological features. Meiotic course is abnormal in almost all the species. The vary basis of the intraspecific genetic diversity, i.e. the variability of chromosome numbers, has been discussed not only for the Western Himalayas taxa, but also on India basis in light of worldwide data, pointing out slight differences in various parameters.
Diferentes ambientes e substratos na formação de mudas de araticum

Low survival rate of araticum seedlings and scarcity of information in scientific literature on proper substrata to araticum (Annona crassiflora Mart.) seedlings production have all been motivating factors to this study. The aim of this paper was to assess the effect of different environments and substrata in the formation of seedlings germinated from araticum seeds. The seeds were treated with gibberellic acid (GA3) (250mg.L -1), being one seed per polypropylene tube measuring 280cm3 at 2 cm deep. Substrata used were medium texture sand (S1), commercial substrate composed by processed and enriched skins, expanded vermiculite, and processed and enriched turf (Plantmax HA) (S2), commercial substrate from granulated coconut fiber (Golden Mix) (S3), medium texture sand + commercial substrate Plantmax HA (1:1; v/v) (S4) and medium texture sand + commercial substrate Golden Mix (1:1; v/v) (S5). The experimental design was in randomized complete blocks, with 5 treatments and 6 repetitions. The experiments were installed in two environments: in the greenhouse and in full sunlight. Data was collected throughout 215 days following sowing. The mortality rate was statistically significant; in S1 the average rate was 18% lower compared to the other substrata. However, the estimated foliar area was smaller on average 0.78cm2. In the greenhouse, emergency in S1 did not differ from the other treatments; notwithstanding, the plant height was on average 0.84 cm shorter when compared to other treatments. Regarding the survival rate, S1 was shown as the best treatment.
Predators control post-fledging mortality in tawny owls, Strix aluco

Despite its recognition as an important source of variation in recruitment probability, the ecological processes leading to mortality between fledging and independence are poorly studied. Accordingly, the proximate and ultimate impact of bottom-up (food limitation) and top-down factors (predators, pathogens) for individual survival as well as population productivity is largely unknown in most terrestrial birds. Survival and behaviour of 131 radio-tagged tawny owls (Strix aluco) during the post-fledging dependency period were studied for each of three years with high food abundance and three years of poor food supply in Danish deciduous woods. To identify the effects of food limitation, 32 young received extra food 2-3 weeks prior to fledging, as opposed to 99 young that were fed by their parents only. Thirty-six percent of the young from control broods died between fledging and independence, primarily due to predation from raptors and mammals (predominantly foxes Vulpes vulpes). Predation by mammals occurred within the first few days after fledging, with young leaving the nest at an early age being at particularly high risk. Young that had received extra food as nestlings were also at higher risk of being preyed upon by mammals, possibly because they were easier to locate on their smell. Total mortality risk (control broods) increased with fledging date from 14% in April to > 58% in June due to an increasing raptor predation risk. Individual attributes such as sex, condition, immunocompetence or prevalence of blood parasites did not predict total or cause-specific mortality risk. Survival during the post-fledging dependency period was therefore primarily a function of variation in predation pressures, particularly from raptors. Increasing raptor predation of late broods appears to be an important selective agent for early breeding in the tawny owl. (Less)
Promoter choice: Who should drive the CAR in T cells?

Chimeric antigen receptor (CAR) T cell therapy is an effective treatment for B cell malignancies, with emerging potential for the treatment of other hematologic cancers and solid tumors. The strength of the promoter within the CAR cassette will alter CAR-polypeptide levels on the cell surface of the T cell – impacting on the kinetics of activation, survival and memory cell formation in T cells. In addition to the CAR, promoters can be used to drive other genes of interest to enhance CAR T cell function. Expressing multiple genes from a single RNA transcript can be effectively achieved by linking the genes via a ribosomal skip site. However, promoters may differ in their ability to transcribe longer RNAs, or could interfere with lentiviral production, or transduction frequencies. In this study we compared the ability of the strong well-characterized promoters CMV, EF-1, hPGK and RPBSA to drive functional expression of a single RNA encoding three products: GFP, CAR, plus an additional cell-survival gene, Mcl-1. Although the four promoters produced similarly high lentiviral titres, EF-1 gave the best transduction efficacy of primary T cells. Major differences were found in the ability of the promoters to drive expression of long RNA encoding GFP, CAR and Mcl-1, highlighting promoter choice as an important consideration for gene therapy applications requiring the expression of long and complex mRNA.
Community structure of the intertidal meiofauna along a gradient of morphodynamic sandy beach types in southern Chile

Se estudiaron tres playas arenosas del sur de Chile (Gaviotas, Guabun y Mar Brava; ca. 42o S) durante el verano del 2000 para analizar los patrones de abundancia y biomasa de la meiofauna a lo largo de un gradiente de tipos morfodinamicos de playas. Se recolectaron muestras de sedimento con cilindros metalicos (23 cm2 de area, 120 cm de longitud) en diez niveles espaciados a intervalos regulares a lo largo de seis transectos separados de 5 a 10 m y extendidos desde un punto sobre el nivel de marea alta y el nivel de marea baja. En cada nivel de muestreo se midio porosidad, fuerza de cizalla, contenido de agua, penetrabilidad y tamano del grano. La meiofauna estuvo primariamente representada por Nematoda y Copepoda Harpacticoidea. Las mayores densidades y biomasas medias por unidad de area se encontraron en la playa reflectiva de Gaviotas (6.172 ind 10 cm-2 y 2,38 g m-2, peso seco libre de cenizas) en comparacion con la playa intermedia de Guabun (3.390 ind 10 cm-2 y 1,70 g m-2) y la playa disipativa de Mar Brava (3.667 ind 10 cm-2 y 0,86 g m-2). La abundancia y biomasa total de la meiofauna por metro lineal de playa (i.e., meiofauna total contenida en un transecto intermareal de 1 m de ancho) fueron mayores en Mar Brava (506 x 106 ind m-1 y 119,4 g m-1) versus Gaviotas (271 x 106 ind m-1 y 101,7 g m-1) y Guabun (143 x 106 ind m-1 y 73,9 g m-1). Por lo tanto, estos ultimos resultados muestran una tendencia de aumento de abundancia y biomasa de la meiofauna intermareal hacia el tipo disipativo dentro del gradiente estudiado de tipos de playas. Los valores mas altos de densidad y biomasa de la meiofauna se encontraron en los niveles superiores y medio de cada playa. En la playa disipativa, se encontro la menor variabilidad en abundancia y biomasa de la meiofauna a lo ancho del intermareal. Segun la prueba de permutacion de Monte Carlo, el contenido de agua, penetrabilidad y tamano del grano fueron las variables que mejor predicen la variabilidad de las densidades de la meiofauna. Los tamanos corporales de nematodos, copepodos, turbelarios, halacaridos y ostracodos estuvieron correlacionados con las caracteristicas del sedimento. En general, las relaciones entre estructura comunitaria de la meiofauna y morfodinamica de playas, fueron similares a aquellas encontradas para la macroinfauna de diferentes playas arenosas alrededor del mundo, lo que sugiere que la meiofauna y macroinfauna son afectadas similarmente por los procesos fisicos asociados a diferentes tipos de playas
Time course of changes in the long latency feedback response parallels the fast process of short term motor adaptation

Adapting to novel dynamics involves modifying both feedforward and feedback control. We investigated whether the motor system alters feedback responses during adaptation to a novel force field in a manner similar to adjustments in feedforward control. We simultaneously tracked the time course of both feedforward and feedback systems via independent probes during a force field adaptation task. Participants (n=35) grasped the handle of a robotic manipulandum and performed reaches to a visual target while the hand and arm were occluded. We introduced an abrupt counter-clockwise velocity-dependent force field during a block of reaching trials. We measured movement kinematics and shoulder and elbow muscle activity with surface EMG electrodes. We tracked the feedback stretch response throughout the task. Using force channel trials we measured overall learning, which was later decomposed into a fast and slow process. We found that the long-latency feedback response (LLFR) was upregulated in the early stages of learning and was correlated with the fast component of feedforward adaptation. The change in feedback response was specific to the long-latency epoch (50-100 ms after muscle stretch) and was observed only in the triceps muscle, which was the muscle required to counter the force field during adaptation. The similarity in time course for the LLFR and the estimated time course of the fast process suggests both are supported by common neural circuits. While some propose that the fast process reflects an explicit strategy, we argue instead that it may be a proxy for the feedback controller. New & Noteworthy We investigated whether changes in the feedback stretch response were related to the proposed fast and slow processes of motor adaptation. We found that the long latency component of the feedback stretch response was upregulated in the early stages of learning, and the time course was correlated with the fast process. While some propose that the fast process reflects an explicit strategy, we argue instead that it may be a proxy for the feedback controller.