Miracle-dz/UniFAR-FTUs huggingface dataset:
Scene statistics and noise determine the relative arrangement of receptive field mosaics

Significance Across a wide variety of species, cells in the retina specialized for signaling either increases (ON) or decreases (OFF) in light represent one of the most basic building blocks of visual computation. These cells coordinate to form mosaics, with each cell responsible for a small, minimally overlapping portion of visual space, but the ways in which these mosaics could be spatially coordinated with each other are relatively unknown. Here, we show how efficient coding theory, which hypothesizes that the nervous system minimizes the amount of redundant information it encodes, can predict the relative spatial arrangement of ON and OFF mosaics. The most information-efficient arrangements are determined both by levels of noise in the system and the statistics of natural images. Many sensory systems utilize parallel ON and OFF pathways that signal stimulus increments and decrements, respectively. These pathways consist of ensembles or grids of ON and OFF detectors spanning sensory space. Yet, encoding by opponent pathways raises a question: How should grids of ON and OFF detectors be arranged to optimally encode natural stimuli? We investigated this question using a model of the retina guided by efficient coding theory. Specifically, we optimized spatial receptive fields and contrast response functions to encode natural images given noise and constrained firing rates. We find that the optimal arrangement of ON and OFF receptive fields exhibits a transition between aligned and antialigned grids. The preferred phase depends on detector noise and the statistical structure of the natural stimuli. These results reveal that noise and stimulus statistics produce qualitative shifts in neural coding strategies and provide theoretical predictions for the configuration of opponent pathways in the nervous system.
Content Analysis of Social Support, and Disease Framing of Klinefelter Syndrome and Down Syndrome: Social Support, Framing and Decision Tendencies

ABSTRACT The Internet plays a crucial role for people searching for health information. In the context of parents faced with a prenatal diagnosis of a chromosomal abnormality, Internet-based resources convey critical information and attitudes that bear on the process of healthcare decision-making. In this study, we collected and analyzed 268 websites for Klinefelter syndrome and Down syndrome, which are two of the most common genetic conditions marked by an abnormal number of chromosomes. While these two syndromes are quite different in terms of their associated symptoms and health consequences, they are commonly screened for, have similar incidence rates, and parents who are presented with prenatal diagnosis of the two conditions terminate pregnancies at similar rates. The study found substantial differences in framings of information, and social support available online for Klinefelter syndrome and Down syndrome. This study’s key finding supports the argument that social support and framing are important mechanisms that mediate online information and perceptions of information utility, hope and decision tendency. The study extends theories and literature related to information framing in a mass media context, social support, and cognitive information processing and applies to investigating online health information, social support and perceptions.
QSAR Modeling Based on Conformation Ensembles Using a Multi-Instance Learning Approach

Modern QSAR approaches have wide practical applications in drug discovery for designing potentially bioactive molecules. If such models are based on the use of 2D descriptors, important information contained in the spatial structures of molecules is lost. The major problem in constructing models using 3D descriptors is the choice of a putative bioactive conformation, which affects the predictive performance. The multi-instance (MI) learning approach considering multiple conformations in model training could be a reasonable solution to the above problem. In this study, we implemented several multi-instance algorithms, both conventional and based on deep learning, and investigated their performance. We compared the performance of MI-QSAR models with those based on the classical single-instance QSAR (SI-QSAR) approach in which each molecule is encoded by either 2D descriptors computed for the corresponding molecular graph or 3D descriptors issued for a single lowest energy conformation. The calculations were carried out on 175 data sets extracted from the ChEMBL23 database. It is demonstrated that (i) MI-QSAR outperforms SI-QSAR in numerous cases and (ii) MI algorithms can automatically identify plausible bioactive conformations.
Shedding Light on the Causes and Characteristics of Stroke in Lebanon: A Systematic Review of Literature

Background: The prevalence and severity of stroke in Lebanon has increased over the past decade and stroke is currently the second leading cause of death in the country. Methods: We systematically reviewed existing research on stroke prevalence, risk factors, mortality and morbidity of stroke, stroke treatment, and stroke education to assess the epidemiology of stroke in Lebanon. A literature search was conducted on the PubMed database for articles presenting data in any of these 5 categories in Lebanon, as well as articles discussing the Middle East and North Africa region generally. Results: A high prevalence of modifiable risk factors (cigarette and waterpipe smoking) and risk factors that could be mitigated by lifestyle changes (obesity and hypertension) were found in Lebanon. Stroke mortality rates and risk factors of mortality were consistent with global trends, though the cost of treatment in Lebanon was significantly higher than in other developing nations. Conclusion: Urgent public health initiatives are needed to educate the public about the dangers of modifiable stroke risk factors and to reduce the burden of stroke in Lebanon.
Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice

Description Pluripotency factor drives cardiogenesis Research indicates that the adult mammalian heart does not contain cardiac stem cells and the vast majority of cardiomyocytes do not divide. Heart regeneration is thus limited after injury. The postmitotic nature of cardiomyocytes blocks cardiac tumor formation but at the same time minimizes cardiomyocyte renewal. Chen et al. report that cell type–specific expression of pluripotency factors dedifferentiates adult cardiomyocytes to a state that resembles fetal cardiomyocytes, enabling adult cardiomyocytes to reenter mitosis (see the Perspective by Wang and Blau). Cardiomyocytes can be reprogrammed to a pluripotent state when expression of pluripotency factors is sustained over an extended period. If cardiomyocytes are only partially reprogrammed, the heart regenerates without tumor formation. —BAP Reversible, cardiomyocyte-specific reprogramming by OCT4, SOX2, KLF4, and c-MYC confers regenerative potential to the mouse heart. Cardiomyocyte (CM) replacement is very slow in adult mammalian hearts, preventing regeneration of damaged myocardium. By contrast, fetal hearts display considerable regenerative potential owing to the presence of less mature CMs that still have the ability to proliferate. In this study, we demonstrate that heart-specific expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) induces adult CMs to dedifferentiate, conferring regenerative capacity to adult hearts. Transient, CM-specific expression of OSKM extends the regenerative window for postnatal mouse hearts and induces a gene expression program in adult CMs that resembles that of fetal CMs. Extended expression of OSKM in CMs leads to cellular reprogramming and heart tumor formation. Short-term OSKM expression before and during myocardial infarction ameliorates myocardial damage and improves cardiac function, demonstrating that temporally controlled dedifferentiation and reprogramming enable cell cycle reentry of mammalian CMs and facilitate heart regeneration.
Protective effects of a small-molecule inhibitor DDQ against tau-induced toxicities in a transgenic tau mouse model of Alzheimer's disease.

The purpose of our study is to determine, DDQ (diethyl (3,4-dihydroxyphenethylamino) (quinolin-4-yl) methylphosphonate) is a newly discovered molecule that has been shown to protect against phosphorylated tau (p-tau) in Alzheimer's disease (ad) pathogenesis. We used a well-studied tau (P301L) transgenic mouse model to achieve our goal. We administered DDQ, into 12-month-old Tau mice, at 20 mg/kg body weight intraperitoneally two times per week for two months. We also assessed DDQ levels in the blood, skeletal muscle, and brain using biochemical and molecular techniques. We investigated the mRNA and protein levels of mitochondrial dynamics, biogenesis, synaptic, p-tau, and longevity genes sirtuins in DDQ-treated tau mice using real time quantitative PCR (q-RT-PCR), immunoblotting, and immunofluorescence techniques. Our extensive pharmacodynamics investigations revealed that skeletal muscle had the greatest peak levels of DDQ, followed by serum and brain. Interestingly, DDQ-treated tau mice had higher levels of mitochondrial fusion, biogenesis, synaptic genes, and sirtuins than DDQ-untreated tau mice. In addition, DDQ-treated tau mice had lower levels of mitochondrial fission and p-tau than untreated tau mice. The current findings, combined with our prior findings, firmly show that DDQ possesses anti-aging, anti-amyloid-beta, and anti-p-tau properties, making it a promising molecule for reducing age-related, amyloid-beta, and p-tau-induced synaptic and mitochondrial toxicities in Alzheimer's disease.
Association between the total amount of electromagnetic cortical neuronal activity and a decline in motivation

In situations involving fatigue, the increase in fatigue levels and the apparent decrease in motivation levels are thought to suppress mental and physical performance to avoid disrupting homeostasis and aid recovery; however, the ultimate source of information on which the brain depends to perceive fatigue and/or a loss of motivation for protection remains unknown. In this study, we found that, as assessed by magnetoencephalography, electromagnetic cortical neuronal activity while performing cognitive tasks was associated with a decrease in motivation caused by the tasks in healthy participants, suggesting the possibility that the brain utilizes information that reflects the invested amount of neural activity to suppress performance. To our knowledge, this is the first report to provide clues for the missing link between neural investments and the resulting activation of the biological alarms that suppress performance.
Effectiveness of interventions for the management of primary frozen shoulder

Aims This systematic review places a recently completed multicentre randomized controlled trial (RCT), UK FROST, in the context of existing randomized evidence for the management of primary frozen shoulder. UK FROST compared the effectiveness of pre-specified physiotherapy techniques with a steroid injection (PTSI), manipulation under anaesthesia (MUA) with a steroid injection, and arthroscopic capsular release (ACR). This review updates a 2012 review focusing on the effectiveness of MUA, ACR, hydrodilatation, and PTSI. Methods MEDLINE, Embase, PEDro, Science Citation Index, Clinicaltrials.gov, CENTRAL, and the World Health Organization (WHO) International Clinical Trials Registry were searched up to December 2018. Reference lists of included studies were screened. No language restrictions applied. Eligible studies were RCTs comparing the effectiveness of MUA, ACR, PTSI, and hydrodilatation against each other, or supportive care or no treatment, for the management of primary frozen shoulder. Results Nine RCTs were included. The primary outcome of patient-reported shoulder function at long-term follow-up (> 6 months and ≤ 12 months) was reported for five treatment comparisons across four studies. Standardized mean differences (SMD) were: ACR versus MUA: 0.21 (95% confidence interval (CI) 0.00 to 0.42), ACR versus supportive care: -0.13 (95% CI -1.10 to 0.83), and ACR versus PTSI: 0.33 (95% CI 0.07 to 0.59) and 0.25 (95% CI -0.34 to 0.85), all favouring ACR; MUA versus supportive care: 0 (95% CI -0.44 to 0.44) not favouring either; and MUA versus PTSI: 0.12 (95% CI -0.14 to 0.37) favouring MUA. None of these differences met the threshold of clinical significance agreed for the UK FROST and most confidence intervals included zero. Conclusion The findings from a recent multicentre RCT provided the strongest evidence that, when compared with each other, neither PTSI, MUA, nor ACR are clinically superior. Evidence from smaller RCTs did not change this conclusion. The effectiveness of hydrodilatation based on four RCTs was inconclusive and there remains an evidence gap. Cite this article: Bone Jt Open 2021;2(9):773–784.
Absence of prostacyclin greatly relieves cyclophosphamide‐induced cystitis and bladder pain in mice

Cyclophosphamide (CP) has been widely used in the treatment of various malignancies and autoimmune diseases, but acrolein, a byproduct of CP, causes severe hemorrhagic cystitis as the major side effect of CP. On the other hand, a large amount of prostacyclin (PGI2) is produced in bladder tissues, and PGI2 has been shown to play a critical role in bladder homeostasis. PGI2 is biosynthesized from prostaglandin (PG) H2, the common precursor of PGs, by PGI2 synthase (PTGIS) and is known to also be involved in inflammatory responses. However, little is known about the roles of PTGIS‐derived PGI2 in bladder inflammation including CP‐induced hemorrhagic cystitis. Using both genetic and pharmacological approaches, we here revealed that PTGIS‐derived PGI2‐IP (PGI2 receptor) signaling exacerbated CP‐induced bladder inflammatory reactions. Ptgis deficiency attenuated CP‐induced vascular permeability and chemokine‐mediated neutrophil migration into bladder tissues and then suppressed hemorrhagic cystitis. Treatment with RO1138452, an IP selective antagonist, also suppressed CP‐induced cystitis. We further found that cystitis‐related nociceptive behavior was also relieved in both Ptgis−/− mice and RO1138452‐treated mice. Our findings may provide new drug targets for bladder inflammation and inflammatory pain in CP‐induced hemorrhagic cystitis.
Prevalence and Correlates of Sex Selling and Sex Purchasing among Adults Seeking Treatment for Cocaine Use Disorder

Abstract Introduction Exchange sex places individuals with cocaine use disorder (CUD) at particularly high risk for deleterious safety and health outcomes. A substance use treatment provider who is aware of a patient’s exchange sex behavior is better able to provide appropriate screening, care, and/or referral to risk reduction services. However, little is known about exchange sex, especially purchasing, among treatment-seeking adults with CUD. Method The current study examined the prevalence and correlates of sex selling and sex purchasing among treatment-seeking men and women with CUD (n = 109; ClinicalTrials.gov #NCT02896712). Separate binary logistic regressions via backward elimination were used to identify best fitting models for sex selling and sex purchasing. Results Over 41% of participants endorsed exchange sex within the last 30 days; 20.2% reported selling sex and 30.3% reported purchasing sex. Sex selling and sex purchasing rates differed by gender and race. Number of sexual partners (OR = 5.83, 95% CI = 2.07–16.43), concern about contracting HIV/AIDS (OR = 2.01, 95% CI = 1.31–3.44), cumulative interpersonal trauma exposure (OR = 1.82, 95% CI = 1.20–2.77), years using cocaine (OR = 1.11, 95% CI = 1.03–1.20), drug-related problem days (OR = 1.07, 95% CI = 1.00–1.14), and sexual preference (OR = 9.50, 95% CI = .69–130.35) were retained in the final model estimating sex selling (Nagelkerke R 2 = .56). In the final sex purchasing model (Nagelkerke R 2 = .46), gender (OR = 36.17, 95% CI = 2.96–441.75), number of sexual partners (OR = 6.28, 95% CI = 2.69–14.66), number of convictions (OR = 1.13, 95% CI = 1.02–1.25), and drug-related problem days (OR = 0.96, 95% CI = .92–1.01) were retained. Conclusion Predictive models in this study identified distinct sets of variables related to sex selling and purchasing. Findings may be used to improve identification of exchange sex in the substance use treatment setting and referral to targeted interventions to reduce associated risk.
Détermination des effets mitochondriaux de la curcumine et de quelques dérivés : proposition d'un mécanisme d'action impliquant le pore de transition de perméabilité

La mitochondrie joue un role cle dans la production des radicaux libres oxygenes (RLO) et dans le processus apoptotique. La premiere partie de ce travail a consiste a etudier les effets mitochondriaux de la curcumine et a revele qu'elle reduisait les productions de RLO et induisait l'ouverture du pore de transition de permeabilite (PTP). Pour comprendre son mecanisme d'action, notre travail a, ensuite, consiste a tester les effets mitochondriaux de 22 derives de la curcumine obtenus par substitution de certaines fonctions chimiques. Cette etude revela que la curcumine et certains derives induisaient l'ouverture du PTP en reduisant l'ion Fe entrainant la production du radical H0 qui oxyde certaines proteines membranaires au niveau de leurs fonctions thiols. D'autre part, cette propriete semble conferee par le groupe phenol associe au groupe methoxy en ortho. Enfin, cette etude a mis en evidence des molecules fortement anti-oxydantes et d'autres potentiellement anti-cancereuses.
Mechanisms and management of 3rd-generation EGFR-TKI resistance in advanced non-small cell lung cancer (Review)

Targeted therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a standard modality of the 1st-line treatments for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC), and substantially improves their prognosis. However, EGFR T790M mutation is the primary mechanism of 1st- and 2nd-generation EGFR-TKI resistance. Osimertinib is a representative of the 3rd-generation EGFR-TKIs that target T790M mutation, and has satisfactory efficacy in the treatment of T790M-positive NSCLC with disease progression following use of 1st- or 2nd-generation EGFR-TKIs. Other 3rd-generation EGFR-TKIs, such as abivertinib, rociletinib, nazartinib, olmutinib and alflutinib, are also at various stages of development. However, the occurrence of acquired resistance is inevitable, and the mechanisms of 3rd-generation EGFR-TKI resistance are complex and incompletely understood. Genomic studies in tissue and liquid biopsies of resistant patients reveal multiple candidate pathways. The present review summarizes the recent findings in mechanisms of resistance to 3rd-generation EGFR-TKIs in advanced NSCLC, and provides possible strategies to overcome this resistance. The mechanisms of acquired resistance mainly include an altered EGFR signaling pathway (EGFR tertiary mutations and amplification), activation of aberrant bypassing pathways (hepatocyte growth factor receptor amplification, human epidermal growth factor receptor 2 amplification and aberrant insulin-like growth factor 1 receptor activation), downstream pathway activation (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) and histological/phenotypic transformations (SCLC transformation and epithelial-mesenchymal transition). The combination of targeted therapies is a promising strategy to treat osimertinib-resistant patients, and multiple clinical studies on novel combined therapies are ongoing.
Deciphering mouse uterine receptivity for embryo implantation at single‐cell resolution

Mice are widely used as an animal model for studying human uterine receptivity for embryo implantation. Although transcriptional changes related to mouse uterine receptivity have been determined by using bulk RNA‐seq, the data are of limited value because the uterus is a complex organ consisting of many cell types. Here, we aimed to decipher mouse uterine receptivity for embryo implantation at single‐cell resolution.
Interindividual and intraindividual variability in amnestic mild cognitive impairment (aMCI) measured with an online cognitive assessment

ABSTRACT Introduction Mean cognitive performance is worse in amnestic mild cognitive impairment (aMCI) compared to control groups. However, studies on variability of cognitive performance in aMCI have yielded inconclusive results, with many differences in variability measures and samples from one study to another. Methods We examined variability in aMCI using an existing older adult sample (n = 91; 51 with aMCI, 40 with normal cognition for age), measured with an online self-administered computerized cognitive assessment (Cogniciti’s Brain Health Assessment). Our methodology extended past findings by using pure measures of variability (controlling for confounding effects of group performance or practice), and a clinically representative aMCI sample (reflecting the continuum of cognitive performance between normal cognition and aMCI). Results Between-group t-tests showed significantly greater between-person variability (interindividual variability or diversity) in overall cognitive performance in aMCI than controls, although the effect size was with a small to moderate effect size, d = 0.44. No significant group differences were found in within-person variability (intraindividual variability) across cognitive tasks (dispersion) or across trials of a response time task (inconsistency), which may be because we used a sample measuring the continuum of cognitive performance. Exploratory correlation analyses showed that a worse overall score was associated with greater inter- and intraindividual variability, and that variability measures were correlated with each other, indicating people with worse cognitive performance were more variable. Discussion The current study demonstrates that self-administered online tests can be used to remotely assess different types of variability in people at risk of Alzheimer`s. Our findings show small but significantly more interindividual differences in people with aMCI. This diversity is considered as “noise” in standard assessments of mean performance, but offers an interesting and cognitively informative “signal” in itself.