Miracle-dz/UniFAR-FTUs huggingface dataset:
Cortical route for facelike pattern processing in human newborns

Significance Newborns show a remarkable ability to detect faces even minutes after birth, an ecologically fundamental skill that is instrumental for interacting with their conspecifics. What are the neural bases of this expertise? Using EEG and a slow oscillatory visual stimulation, we identified a reliable response specific to facelike patterns in newborns, for which underlying cortical sources overlap with the adult face-specific cortical circuit. This suggests that the development of face perception in infants might rely on an early cortical route specialized in face processing already shortly after birth. Humans are endowed with an exceptional ability for detecting faces, a competence that, in adults, is supported by a set of face-specific cortical patches. Human newborns, already shortly after birth, preferentially orient to faces, even when they are presented in the form of highly schematic geometrical patterns vs. perceptually equivalent nonfacelike stimuli. The neural substrates underlying this early preference are still largely unexplored. Is the adult face-specific cortical circuit already active at birth, or does its specialization develop slowly as a function of experience and/or maturation? We measured EEG responses in 1- to 4-day-old awake, attentive human newborns to schematic facelike patterns and nonfacelike control stimuli, visually presented with slow oscillatory “peekaboo” dynamics (0.8 Hz) in a frequency-tagging design. Despite the limited duration of newborns’ attention, reliable frequency-tagged responses could be estimated for each stimulus from the peak of the EEG power spectrum at the stimulation frequency. Upright facelike stimuli elicited a significantly stronger frequency-tagged response than inverted facelike controls in a large set of electrodes. Source reconstruction of the underlying cortical activity revealed the recruitment of a partially right-lateralized network comprising lateral occipitotemporal and medial parietal areas overlapping with the adult face-processing circuit. This result suggests that the cortical route specialized in face processing is already functional at birth.
Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part I: Animal Models and Toxicity Assays

Aims: Experimental retinal research has gained great importance due to the ophthalmic pharmacotherapy era. An increasing number of drugs are constantly released into the market for the treatment of retinal diseases. In this review, animal species, animal models and toxicity assays in retinal research are discussed. Methods: An extensive search of the literature was performed to review various aspects of the methods of investigation of drug toxicity. The different types of animal species, as well as single animal models available for the evaluation of safety and efficacy of retinal pharmacotherapy, were identified. In addition, a large variety of reported laboratory techniques were critically examined. Results: In vitro studies are the first-line experiments for the development of a new drug for retinal diseases, using retinal pigment epithelial cells and other cell lines. The next step involves in vivo animal studies where nonhuman primates are considered the gold standard. However, cost and legal issues make their use difficult. Mice and rats provide genetically controlled models for investigations. Pigs, dogs and cats represent good large-size animal models, while rabbits are one of the most used species for retinal toxicity evaluations. Various laboratory methods were identified, including light microscopy, electron microscopy, electroretinography and new emerging methods, such as optical coherence tomography and scanning laser ophthalmoscopy for experimental purposes. Conclusions: A great number of animal species and models are available that simulate retinal diseases and provide experimental data for further human use. Work with animal models should include properly designed toxicity assays to obtain reliable results for safety and efficacy.
Insufficient Nutrition and Mortality Risk in Septic Patients Admitted to ICU with a Focus on Immune Dysfunction

Immune dysfunction is seen both in sepsis patients and in those with malnutrition. This study aimed to determine whether insufficient nutrition and immune dysfunction have a synergistic effect on mortality in critically ill septic patients. We conducted a prospective observational study from adult sepsis patients admitted to intensive care units (ICUs) between August 2013 and June 2016. Baseline characteristics including age, gender, body mass index, NUTRIC, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were recorded. Immune dysfunction, defined by human leukocyte antigen DR (HLA-DR) expression, was tested at days 1, 3, and 7 of ICU admission. The study included 151 patients with sepsis who were admitted to the ICU. The 28-day survivors had higher day 7 caloric intakes (89% vs. 73%, p = 0.042) and higher day 1-HLA-DR expression (88.4 vs. 79.1, p = 0.045). The cut-off points of day 7 caloric intake and day 1-HLA-DR determined by operating characteristic curves were 65.1% and 87.2%, respectively. Immune dysfunction was defined as patients with day 1-HLA-DR < 87.2%. Insufficient nutrition had no influence on survival outcomes in patients with immune dysfunction. However, patients with insufficient nutrition had poor prognosis when they were immune competent. Insufficient nutrition and immune dysfunction did not have a synergistic effect on mortality in critically ill septic patients.
Various modifications of a vascularized nasoseptal flap for repair of extensive skull base dural defects.

OBJECTIVEEndonasal surgery of the skull base requires watertight reconstruction of the skull base that can seal the dural defect to prevent postoperative CSF rhinorrhea and consequent intracranial complications. Although the incidence of CSF leakage has decreased significantly since the introduction in 2006 of the vascularized nasoseptal flap (the Hadad-Bassagasteguy flap), reconstruction of extensive skull base dural defects remains challenging. The authors describe a new, modified vascularized nasoseptal flap for reconstruction of extensive skull base dural defects.METHODSA retrospective review was conducted on 39 cases from 2010 to 2017 that involved reconstruction of the skull base with an endonasal vascularized flap. Extended nasoseptal flaps were generated by adding the nasal floor and inferior meatus mucosa, inferior turbinate mucosa, or entire lateral nasal wall mucosa. The authors specifically highlight the surgical techniques for flap design and harvesting of these various modifications of the vascularized nasoseptal flap.RESULTSThirty-nine endonasal vascularized flaps were used to reconstruct skull base defects in 37 patients with nonsurgical or postoperative CSF rhinorrhea. Of the 39 procedures, extended nasoseptal flaps were used in 5 cases (13%). These included 2 extended nasoseptal flaps including the inferior turbinate mucosa and 3 extended nasoseptal flaps including the entire lateral nasal wall mucosa. These 5 extended nasoseptal flaps were used in patients who had nonsurgical CSF rhinorrhea due to extensive skull base destruction by invasive pituitary tumors. All flaps healed completely and sealed off the CSF leaks. Olfactory function slightly decreased in the 3 patients with extended nasoseptal flaps including the entire lateral nasal wall mucosa. One patient experienced nasolacrimal duct obstruction, which was treated by dacryocystorhinostomy. The authors encountered no wound complication in this series, while crusting at the donor site required daily nasal toilette and frequent debridement until the completion of mucosalization, which usually takes 8 to 12 weeks after surgery.CONCLUSIONSExtended nasoseptal flaps are a reliable and versatile option that can be used to reconstruct extensive skull base dural defects resulting from destruction by large invasive tumors or complex endoscopic endonasal surgery. An extended nasoseptal flap that includes the entire lateral nasal wall mucosa (360° flap) is the largest endonasal vascularized flap reported to date and may be an alternative for the reconstruction of extensive skull base defects while avoiding the need for additional external approaches.
Investigating the factors underlying adaptive functioning in autism in the EU‐AIMS Longitudinal European Autism Project

Individuals with autism spectrum disorder (ASD) exhibit significant impairments in adaptive functioning that impact on their ability to meet the demands of everyday life. A recurrent finding is that there is a pronounced discrepancy between level of cognitive ability and adaptive functioning, and this is particularly prominent among higher‐ability individuals. However, the key clinical and demographic associations of these discrepancies remain unclear. This study included a sample of 417 children, adolescents, and adults with ASD as part of the EU‐AIMS LEAP cohort. We examined how age, sex, IQ, levels of ASD symptom and autistic trait severity and psychiatric symptomatology are associated with adaptive functioning as measured by the Vineland Adaptive Behavior Scales‐Second Edition and IQ‐adaptive functioning discrepancies. Older age, lower IQ and higher social‐communication symptoms were associated with lower adaptive functioning. Results also demonstrate that older age, higher IQ and higher social‐communication symptoms are associated with greater IQ‐adaptive functioning discrepancy scores. By contrast, sensory ASD symptoms, repetitive and restricted behaviors, as well as symptoms of attention deficit/hyperactivity disorder (ADHD), anxiety and depression, were not associated with adaptive functioning or IQ‐adaptive functioning discrepancy scores. These findings suggest that it is the core social communication problems that define ASD that contribute to adaptive function impairments that people with ASD experience. They show for the first time that sensory symptoms, repetitive behavior and associated psychiatric symptoms do not independently contribute to adaptive function impairments. Individuals with ASD require supportive interventions across the lifespan that take account of social‐communicative ASD symptom severity. Autism Res 2019, 12: 645–657. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.
Cryptic Introgression of Dasypyrum villosum Parental DNA in Wheat Lines Derived from Intergeneric Hybridization

Cytogenetic and DNA molecular analyses have been carried out in 3 wheat introgression lines (ILs; CS×V58, CS×V59, and CS×V60) derived from Triticum aestivum cv. ‘Chinese Spring’ (CS) × Dasypyrum villosum(Dv) intergeneric hybridization. All lines, which showed several phenotypic differences compared to CS, had the same chromosome number (2n = 42) and structure as CS, and neither chromosomes nor chromatin from Dv were apparently added to their complement. However, Feulgen/DNA cytophotometry showed that there was more nuclear DNA in the lines than in the parental wheat (by 1.85%, 2.76%, and 1.26% in CS×V58, CS×V59, and CS×V60, respectively). Molecular investigation indicated the presence of Dv DNA in the ILs. AFLP analysis of genomic DNA from the ILs, CS, and Dv detected a total of 120 polymorphic bands, of which 7 (5.8%) were present in some or all the ILs and Dv but were absent in CS. PCR amplification, sequence analysis of amplicons, and Southern blot hybridization confirmed the presence of Dv-specific sequences in each of the ILs. These results indicate cryptic introgression of Dv DNA sequences into the genome of the ILs. Some implications of this finding are discussed.
Ischemic Postconditioning During Primary Percutaneous Coronary Intervention: The Effects of Postconditioning on Myocardial Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction (POST) Randomized Trial

Background— Ischemic postconditioning has been reported to reduce infarct size in patients with ST-segment–elevation myocardial infarction. However, cardioprotective effects of postconditioning have not been demonstrated in a large-scale trial. Methods and Results— We performed a multicenter, prospective, randomized, open-label, blinded end-point trial. A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction within 12 hours after symptom onset were randomly assigned to the postconditioning group or to the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow as follows: The angioplasty balloon was positioned at the culprit lesion and inflated 4 times for 1 minute with low-pressure (<6 atm) inflations, each separated by 1 minute of deflation. The primary end point was complete ST-segment resolution (percentage resolution of ST-segment elevation >70%) measured at 30 minutes after PCI. Complete ST-segment resolution occurred in 40.5% of patients in the postconditioning group and 41.5% of patients in the conventional PCI group (absolute difference, −1.0%; 95% confidence interval, −8.4 to 6.4; P=0.79). The rate of myocardial blush grade of 0 or 1 and the rate of major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group (17.2% versus 22.4% [P=0.20] and 4.3% versus 3.7% [P=0.70], respectively). Conclusion— Ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment–elevation myocardial infarction undergoing primary PCI with current standard practice. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00942500.
Cryptic conspirators: a conversation about thrombocytopenia and antiphospholipid syndrome

Purpose of review Although antiphospholipid syndrome (APS) is best known for conveying increased risk of thrombotic events and pregnancy morbidity, thrombocytopenia is also recognized as a common association. In this review, we will explore the relationship between thrombocytopenia and APS, highlighting our evolving understanding – and persistent knowledge gaps – through clinically oriented questions and answers. Recent findings A history of thrombocytopenia likely portends a more severe APS phenotype (including increased risk of thrombosis). Although the pathophysiology underlying thrombocytopenia in APS has yet to be definitively revealed, mechanisms that play a role (at least in subsets of patients) include: immune thrombocytopenic purpura/ITP-like autoantibodies against platelet glycoproteins; antiphospholipid antibody (aPL)-mediated platelet activation and consumption; and potentially life threatening thrombotic microangiopathy. Although thrombocytopenia is often ‘mild’ in APS (and therefore, may not require specific therapy), there are causes of acute-onset thrombocytopenia that mandate emergent work-up and treatment. When APS-related thrombocytopenia does require therapy, the approach must be individualized (requiring an understanding of pathophysiology in the particular APS patient). For patients with ITP-like disease, rituximab is emerging as a popular approach to treatment; in contrast, there are hints that thrombopoietin mimetics may be associated with elevated thrombotic risk. Summary Thrombocytopenia is common in APS, and is likely associated with more severe disease. Improved understanding of thrombocytopenia in APS has the potential to improve risk stratification, reveal novel aspects of APS pathophysiology, and lead to treatments that are more individualized and holistic.
Multiscale mechanics of thermal gradient coupled graphene fracture: A molecular dynamics study

The thermo-mechanical coupling mechanism of graphene fracture under thermal gradients possesses rich applications whereas is hard to study due to its coupled non-equilibrium nature. We employ non-equilibrium molecular dynamics to study the fracture of graphene by applying a fixed strain rate under different thermal gradients by employing different potential fields. It is found that for AIREBO and AIREBO-M, the fracture stresses do not strictly follow the positive correlations with the initial crack length. Strain-hardening effects are observed for"REBO-based"potential models of small initial defects, which is interpreted as blunting effect observed for porous graphene. The temperature gradients are observed to not show clear relations with the fracture stresses and crack propagation dynamics. Quantized fracture mechanics verifies our molecular dynamics calculations. We provide a unique perspective that the transverse bond forces share the loading to account for the nonlinear increase of fracture stress with shorter crack length. Anomalous kinetic energy transportation along crack tips is observed for"REBO-based"potential models, which we attribute to the high interatomic attractions in the potential models. The fractures are honored to be more"brittle-liked"carried out using machine learning interatomic potential (MLIP), yet incapable of simulating post-fracture dynamical behaviors. The mechanical responses using MLIP are observed to be not related to temperature gradients. The temperature configuration of equilibration simulation employing the dropout uncertainty neural network potential with a dropout rate of 0.1 is reported to be the most accurate compared with the rest. This work is expected to inspire further investigation of non-equilibrium dynamics in graphene with practical applications in various engineering fields.
Structural brain alterations following adult non-CNS cancers: a systematic review of the neuroimaging literature

Abstract Background: Cancer and cancer treatments may impact the brain through several pathways leading to cognitive impairment. Neuroimaging evidence has begun to elucidate the neurobiological underpinnings of cancer-related cognitive impairment. The aim of this paper was to systematically review available literature on structural brain alterations following adult non-central nervous system (CNS) cancers and associated treatments. Methods: This review followed PRISMA guidelines and was registered in PROSPERO (ID#107387). Comprehensive searches were conducted in June 2018 using PubMed and Web of Science. Inclusion criteria were English peer-reviewed journal articles of formal, controlled studies that examined structural neuroimaging outcomes in adult non-CNS cancer patients and survivors. Selected articles were assessed for quality and risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Thirty-six publications of prospective and cross-sectional studies met inclusion criteria and were included. Structural brain alterations following cancer and its treatment were reported in a majority of the publications as evidenced by reduced global and local gray matter volumes, impaired white matter microstructural integrity, and brain network alterations. Structural alterations were most often evident when cancer-treated groups were compared with healthy controls, and more subtle when compared with cancer controls. Regarding the existence of pretreatment impairments, the evidence was equivocal. There was significant between-study heterogeneity in imaging analytical approaches and use of statistical adjustments. Over half reported associations with cognitive outcomes, though regions and associated cognitive domains were heterogeneous. Conclusions: Structural brain alterations following cancer and cancer treatments were reported in a majority of the reviewed studies. However, the extent of observed alterations depended on the choice of comparison groups. Methodological issues exist that will need to be addressed systematically to ensure the validity of findings. Large-scale prospective studies with extended assessment points are warranted to replicate and build upon initial findings.
Football helmet impact standards in relation to on-field impacts

Youth football helmets currently undergo the same impact testing and must satisfy the same criteria as varsity helmets, although youth football players differ from their adult counterparts in anthropometry, physiology, and impact exposure. This study aimed to relate football helmet standards testing to on-field head impact magnitudes for youth and varsity football helmets. Head impact data, filtered to include only impacts to locations in the current National Operating Committee on Standards for Athletic Equipment standard, were collected for 48 collegiate players (ages 18–23 years) and 25 youth players (ages 9–11 years) using helmet-mounted accelerometer arrays. These on-field data were compared to a series of National Operating Committee on Standards for Athletic Equipment standard drop tests with a youth and varsity Riddell Speed helmet. In the on-field data, the adult players had a higher frequency of impact than the youth players, and a significant difference in head acceleration magnitude only existed at the top location (p < 0.001). In the laboratory drop tests, the only significant difference between the youth and varsity helmets was at the 3.46 m/s (61 cm) impact to the front location (p = 0.0421). Drop tests generated head accelerations within the top 10% of measured on-field impacts, at all locations and drop heights, demonstrating that drop tests are representative of the most severe head impacts experienced by youth and adult football players on the field. Current standards have been very effective at eliminating skull fracture and severe brain injury in both populations. This analysis suggests that there is not currently a need for a youth-specific drop test standard. However, there may be such a need if helmet testing standards are updated to address concussion, paired with a better understanding of differences in concussion tolerance between youth and adult populations.
Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease

Voxelotor (previously GBT440) is a haemoglobin (Hb) modulator that increases Hb‐oxygen affinity, thereby reducing Hb polymerization and sickling of red blood cells (RBCs), being developed as a once‐daily oral drug to treat sickle cell disease (SCD). This first‐in‐human study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of voxelotor in healthy volunteers and SCD patients.