Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential investment in brain regions for a diurnal and nocturnal lifestyle in Australian Myrmecia ants

Animals are active at different times of the day. Each temporal niche offers a unique light environment, which affects the quality of the available visual information. To access reliable visual signals in dim‐light environments, insects have evolved several visual adaptations to enhance their optical sensitivity. The extent to which these adaptations reflect on the sensory processing and integration capabilities within the brain of a nocturnal insect is unknown. To address this, we analyzed brain organization in congeneric species of the Australian bull ant, Myrmecia, that rely predominantly on visual information and range from being strictly diurnal to strictly nocturnal. Weighing brains and optic lobes of seven Myrmecia species, showed that after controlling for body mass, the brain mass was not significantly different between diurnal and nocturnal ants. However, the optic lobe mass, after controlling for central brain mass, differed between day‐ and night‐active ants. Detailed volumetric analyses showed that the nocturnal ants invested relatively less in the primary visual processing regions but relatively more in both the primary olfactory processing regions and in the integration centers of visual and olfactory sensory information. We discuss how the temporal niche occupied by each species may affect cognitive demands, thus shaping brain organization among insects active in dim‐light conditions.
Manipulación (Edición) del genoma del embrión humano ¿un mundo feliz?

Antes de que Bernard pudiera contestar el ascensor se detuvo.iAzotea! Grito una voz estridente-. El ascensorista era una criatura simiesca, que lucia la tunica negra de un semienano EpsilonMenos. iAzotea! -dijo mientras abria las puertas de par en par. La palida luz de la tarde le sobresalto y le obligo a parpadear. iOh azotea! repitio como en extasis. Era como si subita y alegremente hubiese despertado de su sombrio y anonadante sopor-. iAzotea! Con una especie de perruna y expectante adoracion levanto la cara para sonreir a sus pasajeros. Entonces sono un timbre, y desde el techo del ascensor un altavoz empezo, en tono suave pero imperioso, a dictar ordenes. -Baja-dijo-. Baja. Planta decimoctava. Baja, baja. Planta decimoctava. Baja, ba.El ascensorista cerro de golpe las puertas, pulso un boton e inmediatamente se sumergio de nuevo en la luz crepuscular del ascensor; la luz crepuscular de su habitual estupor. En la azotea reinaban la luz y el calor.
Feasibility of the peroral endoscopic myotomy (POEM) procedure with a new small-caliber endoscope (thin-POEM) in patients with achalasia

Abstract Background Peroral endoscopic myotomy (POEM) is a recognized technique for patients with achalasia. We aimed to evaluate the feasibility of using a small-caliber endoscope (thin-POEM) to perform POEM in patients with achalasia. Methods Naïve or previously treated patients were included between February 2016 and April 2018. A small-caliber (5.9 mm) nasoendoscope was used, with a modified closure method using cyanoacrylate. Strict follow-up was performed. Results 45 patients were included, aged 45.5 years (interquartile range [IQR] 22 – 69); 53 % (24/45) had type II achalasia. Median total time for thin-POEM was 54 minutes (IQR 37 – 77) and median myotomy length was 13.5 cm (IQR 6 – 20). Results pre-procedure and 3 months post were Eckardt score 10 vs. 1 (P < 0.001), integrated relaxation pressure (IRP) 25.3 vs. 8.5 mmHg (P < 0.001), and timed barium esophagram (TBE) 100 % severely delayed vs. 86 % normal (P < 0.001), respectively. Type III patients had the longest thin-POEM times (median 58 minutes [IQR 52 – 77]). Reflux was confirmed at 3 months clinically in 17 % of patients, endoscopically in 20 %, and on pH monitoring in 53 %. At 6 months and 12 months, 40 % and 33 % of patients remained positive on pH monitoring and were medically managed. Conclusions Thin-POEM seems to be a safe, effective, and efficient procedure for POEM in patients with achalasia, with good short-term follow-up results.
The Use of Low-Cost Microcomputers as Medium-Fidelity Simulators for Prototype Development, Training and Research

Research time in state-of-the-art flight simulators is in heavy demand. The demand is even more acute when future aircraft and future cockpit systems are the targets of the investigation. Configuring the simulator properly and then training pilots to function in that configuration are substantial time drains. We believe that we have solved many of the problems associated with limiting the cockpit crew station designs to optimal configurations before committing simulator resources to further investigation. Further, we have also resolved a major training requirement in a way that we believe will minimize the need for insimulator training time.
Multi-(myco)toxins in Malting and Brewing By-Products

Fungi, yeasts, and bacteria are common microorganisms on cereals used in malting and brewing industries. These microorganisms are mostly associated with the safety and quality of malt and beer, but also with the health safety of by-products used in animal nutrition. The real problem is their harmful metabolites—toxins that, due to their thermostable properties, can easily be transferred to malting and brewing by-products. Besides fungal metabolites, other toxins originating from plants can be harmful to animal health. Precise and accurate analytical techniques broadened the spectrum of known toxins originating from microorganisms and plants that can pose a threat to animal health. Multi-(myco)toxin analyses are advanced and useful tools for the assessment of product safety, and legislation should follow up and make some important changes to regulate yet unregulated, but highly occurring, microbial and plant toxins in malting and brewing by-products used for animal feed.
Cell‐free DNA as a biomarker of aging

Cell‐free DNA (cfDNA) is present in the circulating plasma and other body fluids and is known to originate mainly from apoptotic cells. Here, we provide the first in vivo evidence of global and local chromatin changes in human aging by analyzing cfDNA from the blood of individuals of different age groups. Our results show that nucleosome signals inferred from cfDNA are consistent with the redistribution of heterochromatin observed in cellular senescence and aging in other model systems. In addition, we detected a relative cfDNA loss at several genomic locations, such as transcription start and termination sites, 5′UTR of L1HS retrotransposons and dimeric AluY elements with age. Our results also revealed age and deteriorating health status correlate with increased enrichment of signals from cells in different tissues. In conclusion, our results show that the sequencing of circulating cfDNA from human blood plasma can be used as a noninvasive methodology to study age‐associated changes to the epigenome in vivo.
Reliability and Agreement of 3D Trunk and Lower Extremity Movement Analysis by Means of Inertial Sensor Technology for Unipodal and Bipodal Tasks

This study evaluates the reliability and agreement of the 3D range of motion (ROM) of trunk and lower limb joints, measured by inertial measurement units (MVN BIOMECH Awinda, Xsens Technologies), during a single leg squat (SLS) and sit to stand (STS) task. Furthermore, distinction was made between movement phases, to discuss the reliability and agreement for different phases of both movement tasks. Twenty healthy participants were measured on two testing days. On day one, measurements were conducted by two operators to determine the within-session and between-operator reliability and agreement. On day two, measurements were conducted by the same operator, to determine the between-session reliability and agreement. The SLS task had lower within-session reliability and agreement compared with between-session and between-operator reliability and agreement. The reliability and agreement of the hip, knee, and ankle ROM in the sagittal plane were good for both phases of the SLS task. For both phases of STS task, within-session reliability and agreement were good, and between-session and between-operator reliability and agreement were lower in all planes. As both tasks are physically demanding, differences may be explained by inconsistent movement strategies. These results show that inertial sensor systems show promise for use in further research to investigate (mal)adaptive movement strategies.
Classification and Quantification of Emphysema Using a Multi-Scale Residual Network

Automated tissue classification is an essential step for quantitative analysis and treatment of emphysema. Although many studies have been conducted in this area, there still remain two major challenges. First, different emphysematous tissue appears in different scales, which we call “inter-class variations. ” Second, the intensities of CT images acquired from different patients, scanners or scanning protocols may vary, which we call “intra-class variations”. In this paper, we present a novel multi-scale residual network with two channels of raw CT image and its differential excitation component. We incorporate multi-scale information into our networks to address the challenge of inter-class variations. In addition to the conventional raw CT image, we use its differential excitation component as a pair of inputs to handle intra-class variations. Experimental results show that our approach has superior performance over the state-of-the- art methods, achieving a classification accuracy of 93.74% on our original emphysema database. Based on the classification results, we also perform the quantitative analysis of emphysema in 50 subjects by correlating the quantitative results (the area percentage of each class) with pulmonary functions. We show that centrilobular emphysema (CLE) and panlobular emphysema (PLE) have strong correlation with the pulmonary functions and the sum of CLE and PLE can be used as a new and accurate measure of emphysema severity instead of the conventional measure (sum of all subtypes of emphysema). The correlations between the new measure and various pulmonary functions are up to |r| = 0.922 (r is correlation coefficient).
Effect of Bone Marrow‐Derived Mesenchymal Stem Cells on Cochlear Function in an Experimental Rat Model

Mesenchymal stem cell (MSC) therapy is an emerging treatment modality for various human diseases. Although induced pluripotent stem cells have been explored for the restoration of hearing, the potential of MSCs as a therapeutic strategy for various cochlear insults is not precisely known. MSCs possess anti‐inflammatory, anti‐apoptotic and neuroprotective properties, making them an attractive target for the treatment of inner ear disorders such as hair cell damage in response to inflammation. Most of the previous studies have used immunosuppression or the complex surgical techniques to deliver stem cells into the cochlea. However, no information is available regarding the biocompatibility and safety of MSCs in the inner ear in immunocompetent cochlea. The aim of the present study was to determine the effect of non‐surgical administration of rodent bone marrow derived MSCs (BM‐MSCs) through transtympanic delivery on the cochlear function and to assess any adverse effects on the auditory system employing a rat model without immunosuppression. We observed that the transtympanic administration of BM‐MSCs has no significant effect on the hearing thresholds as determined by auditory brainstem response and distortion product otoacoustic emissions. Histopathological examination revealed no recruitment of inflammatory leukocytes and edema in the cochlea of BM‐MSCs administrated rats. The results of this study suggest that transtympanic administration of BM‐MSCs is safe and can be explored in providing otoprotection against cochlear insults. Anat Rec, 303:487–493, 2020. © 2019 American Association for Anatomy
Central modulation of parasympathetic outflow is impaired in de novo Parkinson's disease patients

Task- and stimulus-based neuroimaging studies have begun to unveil the central autonomic network which modulates autonomic nervous system activity. In the present study, we aimed to evaluate the central autonomic network without the bias constituted by the use of a task. Additionally, we assessed whether this circuitry presents signs of dysregulation in the early stages of Parkinson’s disease (PD), a condition which may be associated with dysautonomia. We combined heart-rate-variability based methods for time-varying assessments of the autonomic nervous system outflow with resting-state fMRI in 14 healthy controls and 14 de novo PD patients, evaluating the correlations between fMRI time-series and the instantaneous high-frequency component of the heart-rate-variability power spectrum, a marker of parasympathetic outflow. In control subjects, the high-frequency component of the heart-rate-variability power spectrum was significantly anti-correlated with fMRI time-series in several cortical, subcortical and brainstem regions. This complex central network was not detectable in PD patients. In between-group analysis, we found that in healthy controls the brain activation related to the high-frequency component of the heart-rate-variability power spectrum was significantly less than in PD patients in the mid and anterior cingulum, sensorimotor cortex and supplementary motor area, insula and temporal lobe, prefrontal cortex, hippocampus and in a region encompassing posterior cingulum, precuneus and parieto-occipital cortex. Our results indicate that the complex central network which modulates parasympathetic outflow in the resting state is impaired in the early clinical stages of PD.
Chaperone-mediated secretion switching from early to middle substrates in the type III secretion system encoded by Salmonella pathogenicity island 2

The bacterial type III secretion system (T3SS) delivers virulence proteins, called effectors, into eukaryotic cells. T3SS comprises a transmembrane secretion apparatus and a complex network of specialized chaperones that target protein substrates to this secretion apparatus. However, the regulation of secretion switching from early (needle and inner rod) to middle (tip/filament and translocators) substrates is incompletely understood. Here, we investigated chaperone-mediated secretion switching from early to middle substrates in the T3SS encoded by Salmonella pathogenicity island 2 (SPI2), essential for systemic infection. Our findings revealed that the protein encoded by ssaH regulates the secretion of an inner rod and early substrate, SsaI. Structural modeling revealed that SsaH is structurally similar to class III chaperones, known to associate with proteins in various pathogenic bacteria. The SPI2 protein SsaE was identified as a class V chaperone homolog and partner of SsaH. A pulldown analysis disclosed that SsaH and SsaE form a heterodimer, which interacted with another early substrate, the needle protein SsaG. Moreover, SsaE also helped stabilize SsaH and a middle substrate, SseB. We also found that SsaE regulates cellular SsaH levels to translocate the early substrates SsaG and SsaI and then promotes the translocation of SseB by stabilizing it. In summary, our results indicate that the class III chaperone SsaH facilitates SsaI secretion, and a heterodimer of SsaH and the type V chaperone SsaE then switches secretion to SsaG. This is the first report of a chaperone system that regulates both early and middle substrates during substrate switching for T3SS assembly.
Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder

Fetal Alcohol Spectrum Disorder (FASD) is a set of neurodevelopmental malformations caused by maternal consumption of alcohol during pregnancy. FASD sentinel facial features are unique to the disorder, and microcephaly is common in severe forms of FASD. Retinoic acid deficiency has been shown to cause craniofacial malformations and microcephaly in animal models reminiscent of those caused by prenatal alcohol exposure. Alcohol exposure affects the migration and survival of cranial neural crest cells, which are required for proper frontonasal prominence and pharyngeal arch development. Defects in craniofacial development are further amplified by the many downstream pathways that are transcriptionally controlled retinoic acid target genes, including Shh signaling. Recent evidence shows that alcohol exposure itself is sufficient to induce retinoic acid deficiency in the embryo. These data suggest that retinoic acid deficiency is an important underlying etiology of FASD. In disorders like Vitamin A Deficiency, FASD, DiGeorge (22q11.2 Deletion Syndrome), CHARGE, Smith‐Magenis, Matthew‐Wood, and Congenital Zika Syndromes, evidence is accumulating to link reduced retinoic acid signaling with developmental defects like craniofacial malformations and microcephaly. Research focus on characterizing the effects of retinoic acid deficiency during early development and on understanding the downstream signaling pathways involved in aberrant head, and craniofacial development will reveal underlying etiologies of these disorders.
C-reactive protein for diagnosing late-onset infection in newborn infants.

BACKGROUND Late-onset infection is the most common serious complication associated with hospital care for newborn infants. Because confirming the diagnosis by microbiological culture typically takes 24 to 48 hours, the serum level of the inflammatory marker C-reactive protein (CRP) measured as part of the initial investigation is used as an adjunctive rapid test to guide management in infants with suspected late-onset infection. OBJECTIVES To determine the diagnostic accuracy of serum CRP measurement in detecting late-onset infection in newborn infants. SEARCH METHODS We searched electronic databases (MEDLINE, Embase, and Science Citation Index to September 2017), conference proceedings, previous reviews, and the reference lists of retrieved articles. SELECTION CRITERIA We included cohort and cross-sectional studies evaluating the diagnostic accuracy of serum CRP levels for the detection of late-onset infection (occurring more than 72 hours after birth) in newborn infants. DATA COLLECTION AND ANALYSIS Two review authors independently assessed eligibility for inclusion, evaluated the methodological quality of included studies, and extracted data to estimate diagnostic accuracy using hierarchical summary receiver operating characteristic (SROC) models. We assessed heterogeneity by examining variability of study estimates and overlap of the 95% confidence interval (CI) in forest plots of sensitivity and specificity. MAIN RESULTS The search identified 20 studies (1615 infants). Most were small, single-centre, prospective cohort studies conducted in neonatal units in high- or middle-income countries since the late 1990s. Risk of bias in the included studies was generally low with independent assessment of index and reference tests. Most studies used a prespecified serum CRP threshold level as the definition of a 'positive' index test (typical cut-off level between 5 mg/L and 10 mg/L) and the culture of a pathogenic micro-organism from blood as the reference standard.At median specificity (0.74), sensitivity was 0.62 (95% CI 0.50 to 0.73). Heterogeneity was evident in the forest plots but it was not possible to conduct subgroup or meta-regression analyses by gestational ages, types of infection, or types of infecting micro-organism. Covariates for whether studies used a predefined threshold or not, and whether studies used a standard threshold of between 5 mg/L and 10 mg/L, were not statistically significant. AUTHORS' CONCLUSIONS The serum CRP level at initial evaluation of an infant with suspected late-onset infection is unlikely to be considered sufficiently accurate to aid early diagnosis or select infants to undergo further investigation or treatment with antimicrobial therapy or other interventions.
Hypothesis‐driven investigations of diverse pharmacological targets in two mouse models of autism

Autism spectrum disorder is a neurodevelopmental syndrome diagnosed primarily by persistent deficits in social interactions and communication, unusual sensory reactivity, motor stereotypies, repetitive behaviors, and restricted interests. No FDA‐approved medical treatments exist for the diagnostic symptoms of autism. Here we interrogate multiple pharmacological targets in two distinct mouse models that incorporate well‐replicated autism‐relevant behavioral phenotypes. Compounds that modify inhibitory or excitatory neurotransmission were selected to address hypotheses based on previously published biological abnormalities in each model. Shank3B is a genetic model of a mutation found in autism and Phelan‐McDermid syndrome, in which deficits in excitatory neurotransmission and synaptic plasticity have been reported. BTBR is an inbred strain model of forms of idiopathic autism in which reduced inhibitory neurotransmission and excessive mTOR signaling have been reported. The GABA‐A receptor agonist gaboxadol significantly reduced repetitive self‐grooming in three independent cohorts of BTBR. The TrkB receptor agonist 7,8‐DHF improved spatial learning in Shank3B mice, and reversed aspects of social deficits in BTBR. CX546, a positive allosteric modulator of the glutamatergic AMPA receptor, and d‐cycloserine, a partial agonist of the glycine site on the glutamatergic NMDA receptor, did not rescue aberrant behaviors in Shank3B mice. The mTOR inhibitor rapamycin did not ameliorate social deficits or repetitive behavior in BTBR mice. Comparison of positive and negative pharmacological outcomes, on multiple phenotypes, evaluated for replicability across independent cohorts, enhances the translational value of mouse models of autism for therapeutic discovery. GABA agonists present opportunities for personalized interventions to treat components of autism spectrum disorder. Autism Res 2019, 12: 401–421 © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.
Medicaid Accountable Care Organizations and Childbirth Outcomes

Some states have adopted Accountable Care Organization (ACO) models to transform their Medicaid programs, but little is known about their impact on health care outcomes and costs. Medicaid ACOs are uniquely positioned to improve childbirth outcomes because of the number of births covered by Medicaid. Using Healthcare Cost and Utilization Project hospital data, we examined the relationship between ACO adoption and (a) neonatal and maternal outcomes, and (b) cost per birth. We compared outcomes in states that have adopted ACO models in their Medicaid programs with adjacent states without ACO models. Implementation of Medicaid ACOs was associated with a moderate reduction in hospital costs per birth and decreased cesarean section rates. Results varied by state. We found no association between Medicaid ACOs and several birth outcomes, including infant inpatient mortality, low birthweight, neonatal intensive care unit utilization, and severe maternal morbidity. Improving these outcomes may require more time or targeted interventions.