Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying Prokineticin2 as a Novel Immunomodulatory Factor in Diagnosis and Treatment of Sepsis*

OBJECTIVES: Sepsis remains a highly lethal disease, whereas the precise reasons for death remain poorly understood. Prokineticin2 is a secreted protein that regulates diverse biological processes. Whether prokineticin2 is beneficial or deleterious to sepsis and the underlying mechanisms remain unknown. DESIGN: Prospective randomized animal investigation and in vitro studies. SETTING: Research laboratory at a medical university hospital. SUBJECTS: Prokineticin2 deficiency and wild-type C57BL/6 mice were used for in vivo studies; sepsis patients by Sepsis-3 definitions, patient controls, and healthy controls were used to obtain blood for in vitro studies. INTERVENTIONS: Prokineticin2 concentrations were measured and analyzed in human septic patients, patient controls, and healthy individuals. The effects of prokineticin2 on sepsis-related survival, bacterial burden, organ injury, and inflammation were assessed in an animal model of cecal ligation and puncture–induced polymicrobial sepsis. In vitro cell models were also used to study the role of prokineticin2 on antibacterial response of macrophages. MEASUREMENTS AND MAIN RESULTS: Prokineticin2 concentration is dramatically decreased in the patients with sepsis and septic shock compared with those of patient controls and healthy controls. Furthermore, the prokineticin2 concentration in these patients died of sepsis or septic shock is significantly lower than those survival patients with sepsis or septic shock, indicating the potential value of prokineticin2 in the diagnosis of sepsis and septic shock, as well as the potential value in predicting mortality in adult patients with sepsis and septic shock. In animal model, recombinant prokineticin2 administration protected against sepsis-related deaths in both heterozygous prokineticin2 deficient mice and wild-type mice and alleviated sepsis-induced multiple organ damage. In in vitro cell models, prokineticin2 enhanced the phagocytic and bactericidal functions of macrophage through signal transducers and activators of transcription 3 pathway which could be abolished by signal transducers and activators of transcription 3 inhibitors S3I-201. Depletion of macrophages reversed prokineticin2-mediated protection against polymicrobial sepsis. CONCLUSIONS: This study elucidated a previously unrecognized role of prokineticin2 in clinical diagnosis and treatment of sepsis. The proof-of-concept study determined a central role of prokineticin2 in alleviating sepsis-induced death by regulation of macrophage function, which presents a new strategy for sepsis immunotherapy.
Infant repetition effects and change detection: Are they related to adaptive skills?

Repetition effects and change detection response have been proposed as neuro‐electrophysiological correlates of fundamental learning processes. As such, they could be a good predictor of brain maturation and cognitive development. We recorded high density EEG in 71 healthy infants (32 females) aged between 3 and 9 months, while they listened to vowel sequences (standard /a/a/a/i/ [80%] and deviant /a/a/a/a/ [20%]). Adaptive skills, a surrogate of cognitive development, were measured via the parent form of the Adaptive Behavior Assessment System Second Edition (ABAS‐II). Cortical auditory‐evoked potentials (CAEPs) analyses, time‐frequency analyses and a statistical approach using linear mixed models (LMMs) and linear regression models were performed. Age and adaptive skills were tested as predictors. Age modulation of repetition effects and change detection response was observed in theta (3–5 Hz), alpha (5–10 Hz) and high gamma (80–90 Hz) oscillations and in all CAEPs. Moreover, adaptive skills modulation of repetition effects was evidenced in theta (3–5 Hz), high gamma oscillations (80–90 Hz), N250/P350 peak‐to‐peak amplitude and P350 latency. Finally, adaptive skills modulation of change detection response was observed in the N250/P350 peak‐to‐peak amplitude. Our results confirm that repetition effects and change detection response evolve with age. Moreover, our results suggest that repetition effects and change detection response vary according to adaptive skills displayed by infants during the first year of life, demonstrating their predictive value for neurodevelopment.
DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis

DNA methylation is a fundamental epigenetic modification, important across biological processes. The maintenance methyltransferase DNMT1 is essential for lineage differentiation during development, but its functions in tissue homeostasis are incompletely understood. We show that epidermis‐specific DNMT1 deletion severely disrupts epidermal structure and homeostasis, initiating a massive innate immune response and infiltration of immune cells. Mechanistically, DNA hypomethylation in keratinocytes triggered transposon derepression, mitotic defects, and formation of micronuclei. DNA release into the cytosol of DNMT1‐deficient keratinocytes activated signaling through cGAS and STING, thus triggering inflammation. Our findings show that disruption of a key epigenetic mark directly impacts immune and tissue homeostasis, and potentially impacts our understanding of autoinflammatory diseases and cancer immunotherapy.
Survey of Lignin-Structure Changes and Depolymerization during Ionic Liquid Pretreatment

A detailed study of chemical changes in lignin structure during the ionic liquid (IL) pretreatment process is not only pivotal for understanding and overcoming biomass recalcitrance during IL pretreatment but is also necessary for designing new routes for lignin valorization. Chemical changes in lignin were systematically studied as a function of pretreatment temperature, time, and type of IL used. Kraft lignin was used as the lignin source, and common pretreatment conditions were employed using three different ILs of varying chemical structure in terms of acidic or basic character. The chemical changes in the lignin structure due to IL pretreatment processes were monitored using 1H–13C heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR), 31P NMR, elemental analysis, gel permeation chromatography (GPC), and Fourier transform infrared (FT-IR), and the depolymerized products were analyzed using gas chromatography mass spectrometry (GC-MS). Although, with pretreatment in acidic IL,.
Pappus and fruit micromorphology and fruit anatomy in some members of the tribe Cardueae (Asteraceae) from Turkey with their contributions to systematics

The present investigation aims to determine pappus and fruit characters of 21 taxa representing 12 different genera from Turkey. For this reason, present data of pappus and cypsela characters as well as previous results from 21 additional Cardueae taxa have been comparatively evaluated, and a total of 42 taxa were grouped by using cluster and MDS analysis methods. The cluster analysis resolved two main clusters, with five taxa having scale or coroniform pappus as the first‐branching group. Considerable variations were observed in the surface sculpture, and the pericarp and testa anatomical structures as well as the pappus characteristics. On the basis of fruit surface sculpture, four major types and two subtypes of ornamentation patterns were discerned, and based on their anatomies three types of testa epidermal structure were recognized. Our results show that Centaurea s.l. taxa do not exhibit clear distinction from the genus level; in some cases the taxa are separated to some extent, in other cases they are combined with Cyanus and Psephellus taxa. Two Klasea species with sclerenchymatous mesocarp exhibit the closest relationship to Centaurea s.l. taxa. Rhaponticum repens displays the nearest neighborhood with Centaurea s.l. and Klasea taxa. A diagnostic key based on the examined characteristics has been given. The taxonomic importance and systematic implications of the results are discussed in the light of the current framework. The evaluated cypsela and pappus characters are useful not only in assessing relationships within this group but also in delimiting genera and species.
Characterization of Porous Silica Materials with Water at Ambient Conditions. Calculating the Pore Size Distribution from the Excess Surface Work Disjoining Pressure Model

Characterization of mesoporous materials today is routinely performed recording the adsorption isotherm of nitrogen at 77 K. The pore size distribution (PSD) can subsequently be determined using either thermodynamics or statistical mechanics based approaches. While nitrogen has evolved as the reference adsorptive, other gases are often used to extract more information from the isotherm. This contribution is focused on the calculation of a PSD from the water vapor isotherm. It is demonstrated that water adsorption provides accurate results comparable to the standard nitrogen adsorption.
The expression and clinical value of ubiquitin carboxyl-terminal hydrolase L1 in the blood of neonates with hypoxic ischemic encephalopathy

Background Neonatal hypoxic ischemic encephalopathy (HIE) can result in mental retardation due to the associated brain damage. Early identification of brain injury is vital for the prevention and treatment of brain damage in neonates. This study investigated the expression levels of serum ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in neonates with HIE and its correlation with brain damage. Methods From January 2019 to December 2020, 56 cases of neonatal patients with HIE were selected as the observation group, and 60 cases of healthy newborns delivered in our hospital during the same period were selected as the control group. Blood samples were obtained from neonates and the serum expression of UCH-L1 was detected by enzyme-linked immunosorbent assays (ELISAs). The relationship between UCH-L1 and neonatal prognosis and clinical features was analyzed. Results Compared with the healthy control group, the serum levels of UCH-L1 in the observation group was significantly higher (2.28±1.21 vs. 0.81±0.39 ng/mL, P=0.000). Furthermore, at 6 hours after birth, the serum levels of UCH-L1 were significantly higher in neonates with moderate to severe HIE compared to patients with mild HIE (2.92±0.80 and 1.76±0.72 ng/mL, respectively, P=0.000). Pearson correlation analysis showed that the expression levels of UCH-L1 were negatively correlated with the development quotient (DQ), intelligence index (MI), and the Neonatal Behavioral Neurological Assessment (NBNA) score of HIE newborns (P<0.05). Conclusions The level of UCH-L1 protein expression is elevated in the serum of newborns with HIE, and this may have a certain clinical value in predicting the intelligence of children.
Study of COVID-19 Infection, its Severity and Outcome in COVID-19 Vaccinated People at Tertiary Health Care Center, North West Rajasthan.

OBJECTIVE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of corona virus-induced disease 19 (COVID-19) that was declared as a global pandemic in March 2020 by the world health organization (WHO). Two vaccines were granted for emergency use by the Central Drugs Standard Control Organization (CDSCO) in India, Covishield® (AstraZeneca's vaccine manufactured by Serum Institute of India) and Covaxin® (manufactured by Bharat Biotech Limited). Sputnik - V has been granted EUA in the month of April 2021. The purpose of this study is to determine the association of COVID-19 infection, its severity and outcome in COVID-19 vaccinated people. METHODS This was a hospital based prospective cohort study done between March to June 2021 at PBM Associated Group of Hospitals (AGH), Bikaner, Raj. Total 1028 COVID suspected cases consulted in COVID OPD or hospitalized under department of medicine, out of which 146 satisfied the inclusion and exclusion criteria, out of these 146, first 100 cases who gave consent for part of study were selected. RESULTS Among 100 COVID-19 infected cases, 49 received first dose while rest got both doses. After first dose of vaccination 42.86% had mild and 32.65% had severe clinical infection while after both doses 80.39% had mild and 11.76% had severe clinical infection. On evaluation of HRCT Chest, after first dose 8.16% had normal 40.82% were in severe category while those who got both doses it was 52.82% 3.92% respectively. Among 49 who got first dose, 10.20% recovered on just home based treatment without any need of hospitalization, while 89.8% got admitted in dedicated COVID hospital out of which 73.47% got recovered and 16.33% died. Among 51 who got both the doses, 66.67% recovered on just home based treatment, while 33.33% required hospitalization out of which 25.49% got recovered and 7.84% died. CONCLUSION After 2nd dose of vaccine there is a significant risk reduction in need of hospitalization and getting severe infection and mortality when compared with first dose only.
Uncovering the ‘sphinx’ of sphingosine 1‐phosphate signalling: from cellular events to organ morphogenesis

Sphingosine 1‐phosphate (S1P) is a bioactive sphingolipid metabolite, functioning as a signalling molecule in diverse cellular processes. Over the past few decades, studies of S1P signalling have revealed that the physiological activity of S1P largely depends on S1P metabolizing enzymes, transporters and receptors on the plasma membrane, as well as on the intracellular proteins that S1P binds directly to. In addition to its roles in cancer signalling, immunity and inflammation, a large body of evidence has identified a close link of S1P signalling with organ morphogenesis. Here we discuss the vital role of S1P signalling in orchestrating various cellular events during organ morphogenesis through analysing each component along the extracellular and intracellular S1P signalling axes. For each component, we review advances in our understanding of S1P signalling and function from the upstream regulators to the downstream effectors and from cellular behaviours to tissue organization, primarily in the context of morphogenetic mechanisms. S1P‐mediated vesicular trafficking is also discussed as a function independent of its signalling function. A picture emerges that reveals a multifaceted role of S1P‐dependent pathways in the development and maintenance of organ structure and function.
Surface topography index: a novel deformity severity assessment index for pectus excavatum

Background The surface topography index (STI) has great potential in both routine computed tomography (CT) scan and emerging optical imaging systems. However, the diagnostic accuracy and stability of the STI as a deformity severity assessment index has not been fully confirmed. Therefore, the aim of the present study was to determine the diagnostic performance of the STI as a novel deformity severity assessment index for pectus excavatum. Methods The present study consisted of 722 chest CT images from a single center. The standard CT index (CTI) and STI were calculated for all patients. The between-group difference and the level of compliance between the CTI and STI was analyzed by t-test and Pearson correlation. The diagnostic value and optimum discriminatory values of the CTI and STI were calculated by a receiver-operating characteristic (ROC) curve and DeLong’s test. Results The distributions of the CTI and STI were similar and showed a slight overlap between the pectus excavatum (PE) and non-PE groups. Both the CTI and STI significantly differed between the 2 groups (P<0.001). The STI demonstrated a strong Pearson correlation with the CTI (r=0.91, 95% confidence interval: 0.88–0.91, P<0.001). The ROC curves showed that STI =1.58 (sensitivity: 0.93, specificity: 0.95) could be considered equivalent to CTI =2.72 (sensitivity: 0.93, specificity: 0.97) as the optimum discriminatory values. DeLong’s test showed no significant difference in the ROC curve results between the CTI and STI (Z=0.90, P=0.37). Conclusions The STI has comparative discrimination ability in PE diagnosis and deformity severity assessment when used with the standard CTI. The STI as a novel index is not only an ideal evaluation metric of PE deformity but also an objective trait for PE patients just as weight and height for everyone.
A Stable Population Code for Attention in Prefrontal Cortex Leads a Dynamic Attention Code in Visual Cortex

Attention often requires maintaining a stable mental state over time while simultaneously improving perceptual sensitivity. These requirements place conflicting demands on neural populations, as sensitivity implies a robust response to perturbation by incoming stimuli, which is antithetical to stability. Functional specialization of cortical areas provides one potential mechanism to resolve this conflict. We reasoned that attention signals in executive control areas might be highly stable over time, reflecting maintenance of the cognitive state, thereby freeing up sensory areas to be more sensitive to sensory input (i.e., unstable), which would be reflected by more dynamic attention signals in those areas. To test these predictions, we simultaneously recorded neural populations in prefrontal cortex (PFC) and visual cortical area V4 in rhesus macaque monkeys performing an endogenous spatial selective attention task. Using a decoding approach, we found that the neural code for attention states in PFC was substantially more stable over time compared with the attention code in V4 on a moment-by-moment basis, in line with our guiding thesis. Moreover, attention signals in PFC predicted the future attention state of V4 better than vice versa, consistent with a top-down role for PFC in attention. These results suggest a functional specialization of attention mechanisms across cortical areas with a division of labor. PFC signals the cognitive state and maintains this state stably over time, whereas V4 responds to sensory input in a manner dynamically modulated by that cognitive state. SIGNIFICANCE STATEMENT Attention requires maintaining a stable mental state while simultaneously improving perceptual sensitivity. We hypothesized that these two demands (stability and sensitivity) are distributed between prefrontal and visual cortical areas, respectively. Specifically, we predicted attention signals in visual cortex would be less stable than in prefrontal cortex, and furthermore prefrontal cortical signals would predict attention signals in visual cortex in line with the hypothesized role of prefrontal cortex in top-down executive control. Our results are consistent with suggestions deriving from previous work using separate recordings in the two brain areas in different animals performing different tasks and represent the first direct evidence in support of this hypothesis with simultaneous multiarea recordings within individual animals.
Prevalence and factors associated with anxiety, depression and stress in a COVID-19 nursing team.

OBJECTIVE To investigate the levels of anxiety, depression and stress and their associated factors, among nursing professionals who make up the team working against COVID-19 of a University Hospital in the south of Brazil. METHOD Exploratory, descriptive, cross-sectional study conducted from May to July 2020. RESULTS From the total number of professionals, 53.8% had anxiety; 38.4% depression; and 40.3%, stress. Age, length of service in the profession, job satisfaction and work shift showed a statistically significant association with depression, while the employment contract, length of service in the UH, length of service in the unit prior to the opening of the COVID-19 unit and satisfaction at work showed a significant association with stress. CONCLUSIONS The nursing professionals of the COVID-19 team have important levels of anxiety, depression and stress, and the factors associated with depression and stress have been identified.
Functional specificity and neural integration in the aesthetic appreciation of artworks with implied motion

Although there is growing interest in the neural foundations of aesthetic experience, it remains unclear how particular mental subsystems (e.g. perceptual, affective and cognitive) are involved in different types of aesthetic judgements. Here, we use fMRI to investigate the involvement of different neural networks during aesthetic judgements of visual artworks with implied motion cues. First, a behavioural experiment (N = 45) confirmed a preference for paintings with implied motion over static cues. Subsequently, in a preregistered fMRI experiment (N = 27), participants made aesthetic and motion judgements towards paintings representing human bodies in dynamic and static postures. Using functional region‐of‐interest and Bayesian multilevel modelling approaches, we provide no compelling evidence for unique sensitivity within or between neural systems associated with body perception, motion and affective processing during the aesthetic evaluation of paintings with implied motion. However, we show suggestive evidence that motion and body‐selective systems may integrate signals via functional connections with a separate neural network in dorsal parietal cortex, which may act as a relay or integration site. Our findings clarify the roles of basic visual and affective brain circuitry in evaluating a central aesthetic feature—implied motion—while also pointing towards promising future research directions, which involve modelling aesthetic preferences as hierarchical interplay between visual and affective circuits and integration processes in frontoparietal cortex.
Association of nut consumption with risk of total cancer and 5 specific cancers: evidence from 3 large prospective cohort studies.

BACKGROUND The associations between nut consumption and cancer risk have not been extensively investigated. OBJECTIVES We aimed to examine the associations between nut consumption, especially specific types of nuts (peanut, tree nut, walnut, and tree nut other than walnut), and cancer risk. METHODS Nut consumption was assessed by FFQ at baseline and updated every 2-4 y in the Nurses' Health Study (1980-2014), the Nurses' Health Study II (1991-2015), and the Health Professionals Follow-up Study (1986-2018). We examined the associations between the intake of total and specific types of nuts and risk of total cancer and common cancers, including lung, colorectal, breast, bladder, and aggressive prostate cancer. Cox proportional-hazards models were used to obtain the HRs and 95% CIs in each cohort as well as pooled. RESULTS During 5,873,671 person-years of follow-up in 180,832 women and 45,560 men, we documented 44,561 incident cancer cases. As compared with nonconsumers, the pooled multivariable HRs of total nut consumption for ≥5 times/wk were 0.99 (95% CI: 0.94, 1.04; P-trend = 0.54) for total cancer, 0.88 (95% CI: 0.74, 1.04; P-trend = 0.18) for lung cancer, 1.07 (95% CI: 0.92, 1.26; P-trend = 0.89) for colorectal cancer, 0.90 (95% CI: 0.71, 1.14; P-trend = 0.65) for bladder cancer, 0.96 (95% CI: 0.85, 1.08; P-trend = 0.36) for breast cancer, and 1.18 (95% CI: 0.92, 1.51; P-trend = 0.52) for aggressive prostate cancer. CONCLUSIONS In 3 large prospective cohorts, frequent nut consumption was not associated with risk of total cancer and common individual cancers.