Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterising strategy use during the performance of hippocampal-dependent tasks

Recalling the past, thinking about the future and navigating in the world are linked with a brain structure called the hippocampus. Precisely how the hippocampus enables these critical cognitive functions is still debated. The strategies people use to perform tasks associated with these functions have been under-studied, and yet such information could augment our understanding of the associated cognitive processes and neural substrates. Here, we devised and deployed an in-depth protocol to examine the explicit strategies used by 217 participants to perform four naturalistic tasks widely acknowledged to be hippocampal-dependent, namely, those assessing scene imagination, autobiographical memory recall, future thinking and spatial navigation. In addition, we also investigated strategy use for three laboratory-based memory tasks, one of which is held to be hippocampal-dependent – concrete verbal paired associates – and two tasks which are likely hippocampal-independent – abstract verbal paired associates and the dead or alive semantic memory test. We found that scene visual imagery was the dominant strategy not only when mentally imagining scenes, but also during autobiographical memory recall, when thinking about the future and during navigation. Moreover, scene visual imagery strategies were used most frequently during the concrete verbal paired associates task, whereas verbal strategies were most prevalent for the abstract verbal paired associates task and the dead or alive semantic memory task. The ubiquity of specifically scene visual imagery use across a range of tasks may attest to its, perhaps underappreciated, importance in facilitating cognition, whilst also aligning with perspectives that emphasise a key role for the hippocampus in constructing scene imagery.
Neurons need no adaptation to optimally code arbitrarily complex stimuli

Neural networks seem to be able to handle almost any task they face. This feat involves coping efficiently with different data types, at multiple scales, and with varying statistical properties. Here, we show that this so-called optimal coding can occur at the single-neuron level and does not require adaptation. Differentiator neurons, i.e., neurons that spike whenever there is an increase in the input stimuli, are capable of capturing arbitrary statistics and scale of practically any stimulus they encounter. We show this optimality both analytically and using simulations, which demonstrate how an ideal neuron can handle drastically different probability distributions. While the mechanism we present is an oversimplification of “real” neurons and does not necessarily capture all neuron types, this is also its strength since it can function alongside other neuronal goals such as data manipulation and learning. Depicting the simplicity of neural response to complex stimuli, this result may also indicate a straightforward way to improve current artificial neural networks.
Convolutional Neural Networks for Classifying Melanoma Images

In this work, we address the problem of skin cancer classification using convolutional neural networks. A lot of cancer cases early on are misdiagnosed leading to severe consequences including the death of patient. Also there are cases in which patients have other problems and doctors interpret it as skin cancer. This leads to unnecessary time and money spent for further diagnosis. In this work, we address both of the above problems using deep neural networks and transfer learning architecture. We have used publicly available ISIC databases for both training and testing our network. Our model achieves an accuracy of 0.935, precision 0.94, recall 0.77, F1 score 0.85 and ROC-AUC 0.861 which is better than the previous state of the art approaches.
Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping

The newly emergent SARS-CoV-2 coronavirus is closely related to SARS-CoV which emerged in 2002. Studies on coronaviruses in general, and SARS in particular, have identified the virus spike protein (S) as being central to virus tropism, to the generation of a protective antibody response and to the unambiguous detection of past infections. As a result of this centrality SARS-CoV-2 S protein has a role in many aspects of research from vaccines to diagnostic tests. We describe a number of recombinant forms of SARS-CoV-2 S expressed in commonly available expression systems and their preliminary use in diagnostics and epitope mapping. These sources may find use in the current and future analysis of the virus and the Covid-19 disease it causes.
Did I imagine that? The functional role of paracingulate cortex in reality monitoring

Reality monitoring describes our ability to distinguish between internally and externally generated experiences. Individuals show significant variation in this ability and impaired reality monitoring has been linked to the experience of hallucinations. We undertook two studies to investigate the association between reality monitoring and morphology of the paracingulate region of medial prefrontal cortex. In Study 1 we compared reality monitoring accuracy and functional connectivity within paracingulate cortex in groups of healthy controls (N=20) and patients with schizophrenia and hallucinations (N=19). Controls showed greater reality monitoring accuracy that was associated with resting-state functional connectivity between paracingulate, precuneus and occipital cortices, while reality monitoring in patients was associated with more lateral functional connectivity. In Study 2 we used real-time fMRI neurofeedback to obtain causal evidence for the role of the paracingulate cortex in reality monitoring. Healthy individuals received Active feedback from paracingulate cortex (N=21) or Sham feedback based on randomised signal (N=18). Active-group participants showed a specific behavioural effect of improved reality monitoring for Imagined items, as well as increases in both activity within the paracingulate region, and its posterior functional connectivity with precuneus and lateral parietal cortices, and occipital cortex. Our findings suggest reality monitoring in healthy individuals is causally supported by a paracingulate mediated flexible network including the precuneus. Network connectivity can be enhanced using neurofeedback and tracks with improved reality monitoring ability. In contrast, patients with schizophrenia may utilise a distinct and more lateral network which may explain observed sub-optimal reality monitoring accuracy, contributing to the experience of hallucinations. Significance Statement Reality monitoring refers to our ability to distinguish imagination from our experiences in the outside world, and is linked both to hallucinations in schizophrenia as well as to the morphology of paracingulate cortex area of the brain. Here, we revealed less paracingulate involvement in the functional reality monitoring networks in patients with schizophrenia compared to healthy individuals. Thereafter, we used real-time fMRI neurofeedback to show that healthy individuals can learn to upregulate brain activity within the paracingulate cortex, with this resulting in both improved reality monitoring ability and changes in paracingulate functional connectivity. This suggests that paracingulate cortex activity and connectivity play a causal role in reality monitoring, with implications for both the understanding and treatment of hallucinations.
GraphGR: A graph neural network to predict the effect of pharmacotherapy on the cancer cell growth

Genomic profiles of cancer cells provide valuable information on genetic alterations in cancer. Several recent studies employed these data to predict the response of cancer cell lines to treatment with drugs. Nonetheless, due to the multifactorial phenotypes and intricate mechanisms of cancer, the accurate prediction of the effect of pharmacotherapy on a specific cell line based on the genetic information alone is problematic. High prediction accuracies reported in the literature likely result from significant overlaps among training, validation, and testing sets, making many predictors inapplicable to new data. To address these issues, we developed GraphGR, a graph neural network with sophisticated attention propagation mechanisms to predict the therapeutic effects of kinase inhibitors across various tumors. Emphasizing on the system-level complexity of cancer, GraphGR integrates multiple heterogeneous data, such as biological networks, genomics, inhibitor profiling, and genedisease associations, into a unified graph structure. In order to construct diverse and information-rich cancer-specific networks, we devised a novel graph reduction protocol based on not only the topological information, but also the biological knowledge. The performance of GraphGR, properly cross-validated at the tissue level, is 0.83 in terms of the area under the receiver operating characteristics, which is notably higher than those measured for other approaches on the same data. Finally, several new predictions are validated against the biomedical literature demonstrating that GraphGR generalizes well to unseen data, i.e. it can predict therapeutic effects across a variety of cancer cell lines and inhibitors. GraphGR is freely available to the academic community at https://github.com/pulimeng/GraphGR.
Repeat length increases disease penetrance and severity in C9orf72 ALS/FTD BAC transgenic mice

C9orf72 ALS/FTD patients show remarkable clinical heterogeneity, but the complex biology of the repeat expansion mutation has limited our understanding of the disease. BAC transgenic mice were used to better understand the molecular mechanisms and repeat length effects of C9orf72 ALS/FTD. Genetic analyses of these mice demonstrate that the BAC transgene and not integration site effects cause ALS/FTD phenotypes. Transcriptomic changes in cell proliferation, inflammation and neuronal pathways are found late in disease and alternative splicing changes provide early molecular markers that worsen with disease progression. Isogenic sublines of mice with 800, 500 or 50 G4C2 repeats generated from the single-copy C9-500 line show longer repeats result in earlier onset, increased disease penetrance, and increased levels of RNA foci and RAN aggregates. These data demonstrate G4C2 repeat length is an important driver of disease and identify alternative splicing changes as early biomarkers of C9orf72 ALS/FTD.
Seasonal environments drive convergent evolution of a faster pace-of-life in tropical butterflies

Global change can trigger shifts in habitat stability and shape the evolution of organismal life-history strategies, with unstable habitats typically favouring a faster pace-of-life. We test this hypothesis in species-rich Mycalesina butterflies that have undergone parallel radiations in Africa, Asia, and Madagascar. First, our ancestral state reconstruction of habitat preference, using ~85% of extant species, revealed that early forest-linked lineages began to invade seasonal savannahs during the Late Miocene-Pliocene. Second, rearing replicate pairs of forest and savannah species from the African and Malagasy radiation in a common garden experiment, and utilising published data from the Asian radiation, demonstrated that savannah species consistently develop faster, have smaller bodies, higher fecundity with an earlier investment in reproduction, and reduced longevity, compared to forest species across all three radiations. We argue that time-constraints for reproduction favoured the evolution of a faster pace-of-life in savannah species that facilitated their persistence in seasonal habitats.
New insights in biologically active proteins and peptides derived from hen egg

Bioactive peptides are specific protein fragments that positively impact the body's function or condition and ultimately may influence health. These peptides are inactive within the sequence of the parent protein and can be released during proteolysis or fermentation. They may exert a number of different activities in vivo, affecting cardiovascular, endocrine, immune and nervous system in addition to nutrient utilization. Hen eggs have traditionally been recognized as an excellent source of protein, vitamins and minerals. Research in the past decade, however, has produced a substantial amount of evidence indicating that hen egg proteins and peptides may exert several diverse biological effects, above and beyond fulfilling basic nutritional requirements. Several biological activities have now been associated with hen egg proteins, including novel antimicrobial activities, immunomodulatory, anti-cancer, and anti-hypertensive activities, highlighting the importance of hen egg proteins in human health, and disease prevention and treatment. Continued research to identify new and existing biological functions of hen egg proteins and their derivatives will help to define new methods to further improve the value of eggs, as a source of numerous biologically active compounds with specific benefits for human and animal health, and secure their role in the therapy and prevention of chronic and infectious disease.
A new perspective on the evolution of the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors

The most downstream elements of the Hippo pathway, the TEAD transcription factors, are regulated by several cofactors, such as Vg/VGLL1-3. Earlier findings on human VGLL1 and here on human VGLL3 show that these proteins interact with TEAD via a conserved amino acid motif called the TONDU domain. Surprisingly, our studies reveal that the TEAD-binding domain of Drosophila Vg and of human VGLL2 is more complex and contains an additional structural element, an Ω-loop, that contributes to TEAD binding and in vivo function. To explain this unexpected structural difference between proteins from the same family, we propose that, after the genome-wide duplications at the origin of vertebrates, the Ω-loop present in an ancestral VGLL gene has been lost in some VGLL variants. These findings illustrate how structural and functional constraints can guide the evolution of transcriptional cofactors to preserve their ability to compete with other cofactors for binding to transcription factors.
Spinal projections from the medullary reticular formation of the North American opossum: Evidence for connectional heterogeneity

Retrograde and orthograde transport techniques show that the nucleus reticularis gigantocellularis pars ventralis and the nucleus reticularis gigantocellularis project the entire length of the spinal cord. Double‐labelling methods show that some of the neurons in each area innervate both cervical and lumbar levels. There is evidence, however, that neurons in the lateral part of the nucleus reticularis gigantocellularis pars ventralis and the dorsal extreme of the nucleus reticularis gigantocellularis project mainly to cervical and thoracic levels. The autoradiographic method shows that the above nuclei supply direct innervation to somatic and autonomic motor columns as well as to laminae V–VIII and X. The nucleus reticularis gigantocellularis pars ventralis provides additional projections to lamina I and the outer part of lamina II.
Cdk1-dependent destabilization of long astral microtubules is required for spindle orientation

The precise execution of mitotic spindle orientation in response to cell shape cues is important for tissue organization and development. The presence of astral microtubules extending from the centrosome towards the cell cortex is essential for this process, but little is understood about the contribution of astral microtubule dynamics to spindle positioning, or how astral microtubule dynamics are regulated spatiotemporally. The mitotic regulator Cdk1-CyclinB promotes destabilization of centrosomal microtubules and increased microtubule dynamics as cells transition from interphase to mitosis, but how Cdk1 activity specifically modulates astral microtubule stability, and whether it impacts spindle positioning, is unknown. Here we uncover a mechanism revealing that Cdk1 destabilizes astral microtubules to ensure spindle reorientation in response to cell shape. Phosphorylation of the EB1-dependent microtubule plus-end tracking protein GTSE1 by Cdk1 in early mitosis abolishes its interaction with EB1 and recruitment to microtubule plus-ends. Loss of Cdk1 activity, or mutation of phosphorylation sites in GTSE1, induces recruitment of GTSE1 to growing microtubule plus-ends in mitosis. This decreases the catastrophe frequency of astral microtubules, and causes an increase in the number of long astral microtubules reaching the cell cortex, which restrains the ability of cells to reorient spindles along the long cellular axis in early mitosis. Astral microtubules must thus not only be present, but also dynamic to allow the spindle to reorient in response to cell shape, a state achieved by selective destabilization of long astral microtubules via Cdk1.
Toxicity of nano-anatase TiO2 to mice: Liver injury, oxidative stress

There are concerns regarding the toxicity of nano-TiO2, but data are limited on the mechanism underlying oxidative damage to liver of mice. In order to further study these mechanisms of nano-TiO2 particles, nano-anatase TiO2 (5 nm) were injected into the abdominal cavity of ICR mice daily for 14 days and biochemical parameters in liver were investigated. The increase of hepatic lipids peroxide produced by nano-anatase TiO2 suggested an oxidative attack that was activated by a reduction of antioxidative defense mechanisms as measured by analyzing the activities of superoxide dismutase, catalase, ascorbate peroxidase, and glutathione peroxidase, as well as antioxidant levels such as glutathione and ascorbic acid. The antioxidative responses of liver were reduced in mice by nano-anatase TiO2. The oxidative stress of nano-anatase TiO2 on liver was greater than that seen with bulk-TiO2.
Dactinomycin in acute myeloid leukemia with NPM1 mutations.

OBJECTIVES Complete responses have been observed in NPM1-mutated AML patients with dactinomycin, a nucleolar stress-inducing drug. Here, we report a single-center experience of compassionate use of dactinomycin in untreated or relapsed/ refractory NPM1-mutated AML. METHODS From September 2015 to February 2019, 26 adult patients with NPM1-mutated AML received dactinomycin in different situations: front-line treatment in 4 unfit patients (16%); morphologic (n = 16, 62%), molecular relapses (n = 4, 16%), refractory disease (n = 1, 13%), or postremission therapy in second complete response (n = 1, 13%). RESULTS Median age was 62.5 years. Median number of dactinomycin cycle was 1 (1-8), and 7 patients (27%) received more than 3 cycles. Three out of 17 patients (18%) in morphologic relapse or refractory to chemotherapy achieved complete remission after the first cycle of dactinomycin. None of the 4 patients unfit for intensive chemotherapy responded to dactinomycin as front-line therapy. Grade 3-4 adverse events were thrombocytopenia (n = 11, 42%), neutropenia (n = 11, 42%), GI toxicity (n = 6, 23%), mucositis (n = 5, 19%), lung infection (n = 5, 19%), and skin rash (n = 2, 7.6%). CONCLUSIONS Dactinomycin is an inexpensive and easily available drug that may induce significant responses in few AML patients with NPM1 mutations with an acceptable safety profile.
THE USE OF A PERCOLATION TECHNIQUE IN STUDYING ANTIBIOTIC PRODUCTION IN SOIL

The adaptation of a percolation technique to the study of the production of antibiotics in soil is described. Antibiotic activity is determined by assays of a continuously circulating soil solution without disturbing the soil sample itself. The advantages of this technique over existing methods of study are discussed. Results are presented illustrating the production of antibiotics in sterile soil by a Penicillium sp. and two unidentified Streptomyces spp.
Congenital toxoplasmosis: What is the evidence for chemoprophylaxis to prevent fetal infection?

Although prenatal diagnosis and prenatal and neonatal therapy of congenital toxoplasmosis are available, there is controversy concerning the effectiveness of prophylaxis to prevent placental transmission. Experimental, parasitological, and clinical data suggest a “window of opportunity” following maternal infection. Among medications active against Toxoplasma gondii, mainly spiramycin (Spy) and pyrimethamine + sulfonamide combinations (P‐S) have been evaluated. Results from observational studies suffered treatment bias, since prescriptions differed according to the gestational age at seroconversion, which is the major risk factor for transmission, and many lacked precise timing. Some large retrospective studies found no difference in transmission according to prophylactic treatment, but transmission was lower when treatment started promptly after maternal seroconversion. A few recent studies adjusting for timing of infection observed lower transmission in case of P‐S than other or no prophylaxis. In the only randomized controlled trial, transmission was lower with P‐S than S (18.5% vs 30%, P = .147); this association was strengthened when the treatment was started within 3 weeks of seroconversion, and the incidence of fetal cerebral ultrasound signs was significantly reduced in the P‐S group. Rapid initiation of prophylactic therapy following maternal infection, which is usually asymptomatic, requires systematic screening for maternal seroconversion during pregnancy.
Healthcare Resource Utilization and Management of Chronic, Refractory Low Back Pain in the United States.

STUDY DESIGN Retrospective analysis of inpatient and outpatient medical insurance claims data from a database containing over 100 million individuals. OBJECTIVE To quantify the healthcare resource utilization (HCRU) of non-surgical treatments in the first 2 years after a chronic, refractory low back pain (CRLBP) diagnosis. SUMMARY OF BACKGROUND DATA Patients with persistent low back pain (LBP) despite conventional medical management and who are not candidates for spine surgery are considered to have chronic, refractory low back pain (CRLBP) and incur substantial healthcare costs over time. Few data exist on the HCRU of this specific population. METHODS The IBM MarketScan Research databases from 2009 to 2016 were retrospectively analyzed to identify US adults with a diagnosis of non-specific LBP and without cancer, spine surgery, failed back surgery syndrome, or recent pregnancy. We required > 30 days of utilization of pain medications or non-pharmacologic therapies within both the 3-12- and 12-24-month periods post-diagnosis. Annual total healthcare costs, costs subdivided by insurance type, and use of non-surgical therapies were determined for 2 years after diagnosis of LBP. RESULTS 55,945 patients with CRLBP were identified. Median total cost was $6,590 (Q1 $2,710, Q3 $13,922) in the first year, almost doubling the baseline cost; costs were highest for patients with Medicare Supplemental insurance, reaching $10,156 (Q1 $5,481, Q3 $18,570). 33,664 (60.2%) patients engaged physical therapy, 28,016 (50.1%) engaged chiropractors, and 14,488 (25.9%) had steroid injections. 36,729 (65.7%) patients used prescription pain medications, most commonly opioids (N = 31,628, 56.5%) and muscle relaxants (N = 21,267, 38.0%). CONCLUSION This study is one of the first to investigate the HCRU of a large, longitudinal US cohort of patients with CRLBP. These patients experience substantial healthcare costs. Contrary to LBP management guidelines, most patients used opioids, and several non-pharmacologic therapies were used by only a few patients. LEVEL OF EVIDENCE 3.