Miracle-dz/UniFAR-FTUs huggingface dataset:
SpO2/FiO2 as a predictor of non-invasive ventilation failure in children with hypoxemic respiratory insufficiency

Abstract Generally, monitoring of hypoxemia has been always based on partial pressure of arterial oxygen to fraction of inspired oxygen ratio; recently it was confirmed a good correlation between this ratio and a non-invasive alternative ratio of oxygen saturation to fraction of inspired oxygen (SF ratio = SpO2/FiO2). The SF ratio has been studied and validated, especially in the intubated patients, however studies monitoring patients treated with non-invasive ventilation (NIV) are lacking. The aim of the study was to determine if the SF ratio is a reliable predictive factor for failure of NIV in pediatric patients diagnosed with hypoxemic acute respiratory failure due to pneumonia. A five year retrospective study with consecutive sampling of patients diagnosed with hypoxemic acute respiratory failure due to pneumonia, admitted to the pediatric intensive care unit in a university hospital and treated with NIV was conducted. Physiological and ventilator variables were collected before starting NIV and at 2, 8 and 12 hours of treatment, and the corresponding SF ratios calculated. Thirty-four patients were studied. NIV failed in seven patients. Significant differences in SF ratio were observed between the successful and unsuccessful patients at the onset, 2 and 12 hours of treatment. Multivariable analysis revealed the SF ratio at two hours to be an independent predictor of NIV failure (odds ratio = 0.96, 95% confidence intervals 0.93–0.99; P = 0.015). Area Under Receiver Operating Characteristic curve = 0.90 (95% confidence interval = 0.79 to 1.000), optimal cut off value for SF at 2 hours ≤ 189; sensitivity = 86%, specificity = 74%. In conclusion, the SF ratio of 189 or less at 2 hours of NIV seems to be useful for predicting NIV failure in this cohort.
Phase II Trial of Ipilimumab with Stereotactic Radiation Therapy for Metastatic Disease: Outcomes, Toxicities, and Low-Dose Radiation–Related Abscopal Responses

Determining combination therapies to improve immune checkpoint blockade can benefit patient outcome. In a phase II clinical trial, ipilimumab plus stereotactic radiotherapy provides clinical benefit to metastatic cancer patients. Ipilimumab is effective for patients with melanoma, but not for those with less immunogenic tumors. We report a phase II trial of ipilimumab with concurrent or sequential stereotactic ablative radiotherapy to metastatic lesions in the liver or lung (NCT02239900). Ipilimumab (every 3 weeks for 4 doses) was given with radiotherapy begun during the first dose (concurrent) or 1 week after the second dose (sequential) and delivered as 50 Gy in 4 fractions or 60 Gy in 10 fractions to metastatic liver or lung lesions. In total, 106 patients received ≥1 cycle of ipilimumab with radiation. Median follow-up was 10.5 months. Median progression-free survival time was 2.9 months (95% confidence interval, 2.45–3.40), and median overall survival time was not reached. Rates of clinical benefit of nonirradiated tumor volume were 26% overall, 28% for sequential versus 20% for concurrent therapy (P = 0.250), and 31% for lung versus 14% for liver metastases (P = 0.061). The sequential lung group had the highest rate of clinical benefit at 42%. There were no differences in treatment-related adverse events between groups. Exploratory analysis of nontargeted lesions revealed that lesions receiving low-dose radiation were more likely to respond than those that received no radiation (31% vs. 5%, P = 0.0091). This phase II trial of ipilimumab with stereotactic radiotherapy describes satisfactory outcomes and low toxicities, lending support to further investigation of combined-modality therapy for metastatic cancers.
Antiglycation Activity of Aucubin In Vitro and in Exogenous Methylglyoxal Injected Rats

Advanced glycation end products (AGEs) is a causative factor of various chronic diseases, including chronic kidney disease and atherosclerosis. AGE inhibitors, such as aminoguanidine and pyridoxamine, have the therapeutic activities for reversing the increase in AGEs burden. This study evaluated the inhibitory effects of aucubin on the formation of methylglyoxal (MGO)-modified AGEs in vitro. We also determined the potential activity of aucubin in reducing the AGEs burden in the kidney, blood vessel, heart, and retina of exogenously MGO-injected rats. Aucubin inhibited the formation of MGO-modified AGE-bovine serum albumin (IC50 = 0.57 ± 0.04 mmol/L) and its cross-links to collagen (IC50 = 0.55 ± 0.02 mmol/L) in a dose-dependent manner. In addition, aucubin directly trapped MGO (IC50 = 0.22 ± 0.01 mmol/L) in vitro. In exogenous MGO-injected rats, aucubin suppressed the formation of circulating AGEs and its accumulation in various tissues. These activities of aucubin on the MGO-derived AGEs in vitro and in vivo showed its pharmacological potential for inhibiting AGEs-related various chronic diseases.
Total-Factor Eco-Efficiency and Its Influencing Factors in the Yangtze River Delta Urban Agglomeration, China

Urban agglomerations are not only the core areas leading economic growth but also the fronts facing severe resource and environmental challenges. This paper aimed to increase our understanding of urban eco-efficiency and its influencing factors and thus provide the scientific basis for green development. We developed a model that incorporates super-efficiency, slacks-based-measure, and global-frontier technology to calculate the total-factor eco-efficiency (TFEE) and used a spatial panel Tobit model to take into account spatial spillover effects. An empirical study was conducted utilizing a prefecture-level dataset in the Yangtze River Delta Urban Agglomeration (YRDUA) from 2003 to 2016. The main findings reveal that significant spatial differences exist in TFEE in the YRDUA: high-TFEE cities were majorly located in the coastal areas, while low-TFEE cities were mostly situated inland. Overall, TFEE shows a trend of “decline first and then rise with fluctuation”; the disparity between inland and coastal regions has expanded. Further regression analysis suggests that industrial structure, environmental regulation, and innovation were positively related to TFEE, while foreign direct investment was not conducive to the growth in TFEE. The relationship between population intensity and urban eco-efficiency is an inverted U-shaped curve. Finally, several specific policy implications were raised based on the results.
White matter tract myelin maturation and its association with general psychopathology in adolescence and early adulthood

Adolescence is a time period associated with marked brain maturation that coincides with an enhanced risk for onset of psychiatric disorder. White matter tract myelination, a process that continues to unfold throughout adolescence, is reported to be abnormal in several psychiatric disorders. Here, we ask whether psychiatric vulnerability is linked to aberrant developmental myelination trajectories. We assessed a marker of myelin maturation, using magnetisation transfer (MT) imaging, in 10 major white matter tracts. We then investigated its relationship to the expression of a general psychopathology “p‐factor” in a longitudinal analysis of 293 healthy participants between the ages of 14 and 24. We observed significant longitudinal MT increase across the full age spectrum in anterior thalamic radiation, hippocampal cingulum, dorsal cingulum and superior longitudinal fasciculus. MT increase in the inferior fronto‐occipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus was pronounced in younger participants but levelled off during the transition into young adulthood. Crucially, longitudinal MT increase in dorsal cingulum and uncinate fasciculus decelerated as a function of mean p‐factor scores over the study period. This suggests that an increased expression of psychopathology is closely linked to lower rates of myelin maturation in selective brain tracts over time. Impaired myelin growth in limbic association fibres may serve as a neural marker for emerging mental illness during the course of adolescence and early adulthood.
Retinotopic specializations of cortical and thalamic inputs to area MT

Significance Foveal specializations in the primate visual system have allowed for high-acuity vision and are crucial to the evolution of the brain and primate behaviors. Here we show that the dorsal visual stream, which is dedicated to processing visual motion and visually guided behaviors, comprises foveal specializations. We report that spiny stellate cells, an anatomically specialized type of projection neuron, are distributed mainly in the foveal portion of the primary visual cortex (V1)-middle temporal area (MT) pathway. Moreover, we demonstrate that the thalamic input to the MT area from the medial inferior pulvinar is organized in a retinotopic manner. These results change our understanding of the anatomic organization of the early visual system. Retinotopic specializations in the ventral visual stream, especially foveal adaptations, provide primates with high-acuity vision in the central visual field. However, visual field specializations have not been studied in the dorsal visual stream, dedicated to processing visual motion and visually guided behaviors. To investigate this, we injected retrograde neuronal tracers occupying the whole visuotopic representation of the middle temporal (MT) visual area in marmoset monkeys and studied the distribution and morphology of the afferent primary visual cortex (V1) projections. Contrary to previous reports, we found a heterogeneous population of V1-MT projecting neurons distributed in layers 3C and 6. In layer 3C, spiny stellate neurons were distributed mainly in foveal representations, while pyramidal morphologies were characteristic of peripheral eccentricities. This primate adaptation of the V1 to MT pathway is arranged in a way that we had not previously understood, with abundant stellate projection neurons in the high-resolution foveal portions, suggesting rapid relay of motion information to visual area MT. We also describe that the medial portion of the inferior pulvinar (PIm), which is the main thalamic input to area MT, shows a retinotopic organization, likely reflecting the importance of this pathway during development and the establishment of area MT topography.
Dihydroartemisinin attenuates lipopolysaccharide-induced acute lung injury in mice by suppressing NF-κB signaling in an Nrf2-dependent manner

Acute lung injury (ALI) is a severe health issue with significant morbidity and mortality. Artemisinin is used for the treatment of fever and malaria in clinical practice. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, plays a role in anti-organizational fibrosis and anti-neuronal cell death. However, whether DHA can attenuate ALI remains unclear. The current study thus examined the effects of DHA on ALI and primary macrophages. The results revealed that DHA attenuated lipopolysaccharide (LPS)-induced pulmonary pathological damage. DHA suppressed the LPS-induced infiltration of inflammatory cells, the elevation of myeloperoxidase activity, oxidative stress and the production of pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and IL-6. Furthermore, DHA reduced the LPS-induced inflammatory response by suppressing the degradation of I-κB and the nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)/p65 in vivo and in vitro. DHA activated the nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway, which was suppressed by LPS treatment. The Nrf2 inhibitor, ML385, diminished the protective effects of DHA against LPS-induced inflammation in macrophages. On the whole, the findings of this study demonstrate that DHA exerts therapeutic effects against LPS-induced ALI by inhibiting the Nrf2-mediated NF-κB activation in macrophages. The present study also confirmed the therapeutic effects of DHA in mice with LPS-induced ALI. Thus, these findings demonstrate that DHA exhibits anti-inflammatory activities and may be a therapeutic candidate for the treatment of ALI.
Injury-Related Behavioral Variables in Alpine Skiers, Snowboarders, and Ski Tourers—A Matched and Enlarged Re-Analysis

Behavioral variables might play an important role in explaining the differences in injury rates across winter sport disciplines and injury prevention programs might be more specifically designed based on this knowledge. On ski slopes, alpine skiing, snowboarding, and ski touring are the predominant winter sport disciplines. Therefore, the aim of the present study was to investigate possible differences in injury-related behavioral variables between practitioners of these disciplines. Using a matched re-analysis approach of a cross-sectional survey, 414 winter sport participants (alpine skiers, snowboarders, ski tourers, each n = 138) were analyzed on the differences in sensation seeking, treated injuries, and injury-related behavioral variables. Cochran–Mantel–Haenszel and Friedman tests revealed significantly higher sensation seeking, p < 0.001, and a significantly higher percentage of participants reporting to have consumed alcohol in the past five skiing days, p = 0.006, in snowboarders compared to alpine skiers. The participants with treated injuries showed higher sensation seeking, p < 0.050, and a higher percentage of snowboarders, p = 0.020, compared to participants without treated injuries. Injury prevention programs for snowboarders, who remain an important risk group for injury prevention, might benefit from considering a possibly higher percentage of alcohol-consuming participants and from providing information on injury-related risks of sensation seeking.
Improving care home design for people with dementia

With more people with dementia living in care homes in the UK than ever before, there is growing recognition that the design of such internal and external spaces should meet dementia friendly principles. This paper reports on one part of a study to evaluate the reliability and validity of two tools: The Design Audit Tool and the Environmental Audit Tool developed to audit how dementia-friendly internal and external environments (specifically care homes) are for people with dementia, and presents a qualitative analysis of the reports presented to care homes following each audit. Thirty care homes took part in the study to evaluate the design audit tools and, following good practice, received a home report detailing up to five design strengths and five limitations following the audit. Analysis of the home reports identifies variation and variability in meeting dementia-friendly principles as specified by both tools. Areas of variability included wayfinding, the use of colour and contrast, access to outside spaces, individualization of personal and communal spaces, lighting and opportunities to engage with the environment. This paper provides valuable insights into variability in care home design and identifies common areas of weakness and strength in care homes of different type, ownership and localities.
Optimal Consumption and Investment Strategies under Wealth Ratcheting

Individuals driven by capital accumulation may be reluctant to experience large wealth downfalls. Implications for optimal consumption and investment policies are explored in a dynamic setting where wealth is restrained from falling below a fraction of its all-time high. Risky investment regulates wealth growth and mitigates the ratchet effect of the constraint, and may decrease as wealth approaches its maximum. The correspondence found between habit formation over consumption and wealth ratcheting provides a rational explanation for the extensive use of such a practice in investment management. An extension embeds the spirit of capitalism using wealth as an index for social status. JEL Classification: D81, E21, G11
Carbon and nitrogen isotopic variability in foxtail millet (Setaria italica) with watering regime

Rationale Carbonised plant remains are analysed for reconstruction of past climates and agricultural regimes. Several recent studies have used C4 plants to address related questions, and correlations between modern C4 plant δ13C values and rainfall have been found. The millets were important food crops in prehistoric Eurasia, yet little is known about causes of isotopic variation within millet species. Previous research has shown there to be significant isotopic variation between millet accessions. Here we compare isotope ratios from plants grown under different watering regimes. This allows for a consideration of whether or not Setaria italica is a good proxy for environmental reconstruction. Methods We compare stable isotope ratios of Setaria italica plants grown in a controlled environment chamber with different watering regimes. We compare the carbon isotope ratios of leaves and grains, and the nitrogen isotope ratios of grains, from 12 accessions of Setaria italica. Results We find significant isotopic variability between watering regimes. Carbon isotope ratios are positively correlated with water availability, and on average vary by 1.9‰ and 1.7‰ for leaves and grains, respectively. Grain nitrogen isotope ratios also vary with watering regime; however, the highest isotope ratios are found with the 130‐mL watering regime. Conclusions The carbon isotope ratios of Setaria italica are strongly correlated with water availability. However, the correlation is the opposite to that seen in studies of C3 plants. The difference in isotopic ratio due to watering regime is comparable with that seen between different accessions; thus distinguishing between changing varieties of Setaria italica and changing climate is problematic. In terms of grain nitrogen isotope ratios, the highest δ15N values were not associated with the lowest watering regime. Again, δ15N variation is comparable with that which would be expected from an aridity effect or a manuring effect, and thus distinguishing between these factors is probably problematic.
Comparison of Different Invasive and Non-Invasive Methods to Characterize Intestinal Microbiota throughout a Production Cycle of Broiler Chickens

In the short life of broiler chickens, their intestinal microbiota undergoes many changes. To study underlying biological mechanisms and factors that influence the intestinal microbiota development, longitudinal data from flocks and individual birds is needed. However, post-mortem collection of samples hampers longitudinal data collection. In this study, invasively collected cecal and ileal content, cloacal swabs collected from the same bird, and boot sock samples and cecal droppings from the litter of the broilers’ poultry house, were collected on days 0, 2, 7, 14 and 35 post-hatch. The different sample types were evaluated on their applicability and reliability to characterize the broiler intestinal microbiota. The microbiota of 247 samples was assessed by 16S ribosomal RNA gene amplicon sequencing. Analyses of α and β measures showed a similar development of microbiota composition of cecal droppings compared to cecal content. Furthermore, the composition of cecal content samples was comparable to that of the boot socks until day 14 post-hatch. This study shows that the value of non-invasive sample types varies at different ages and depends on the goal of the microbiota characterization. Specifically, cecal droppings and boot socks may be useful alternatives for cecal samples to determine intestinal microbiota composition longitudinally.
Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial.

PURPOSE To independently validate two biomarkers, a 44-gene DNA damage immune response (DDIR) signature and stromal tumor-infiltrating lymphocytes (sTILs), as prognostic markers in patients with triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin (A) and cyclophosphamide (C) in SWOG 9313. METHODS Four hundred twenty-five centrally determined patient cases with TNBC from S9313 were identified. DDIR signature was performed on RNA isolated from formalin-fixed paraffin-embedded tumor tissue, and samples were classified as DDIR negative or positive using predefined cutoffs. Evaluation of sTILs was performed as described previously. Markers were tested for prognostic value for disease-free survival (DFS) and overall survival (OS) using Cox regression models adjusted for treatment assignment, nodal status, and tumor size. RESULTS Among 425 patients with TNBC, 33% were node positive. DDIR was tested successfully in 90% of patients (381 of 425), 62% of which were DDIR signature positive. DDIR signature positivity was associated with improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.92; P = .015) and OS (HR, 0.61; 95% CI, 0.43 to 0.89; P = .010). sTILs density assessment was available in 99% of patients and was associated with improved DFS (HR, 0.70; 95% CI, 0.51 to 0.96; P = .026 for sTILs density ≥ 20% v < 20%) and OS (HR, 0.59; 95% CI, 0.41 to 0.85; P = .004 for sTILs density ≥ 20% v < 20%). DDIR signature score and sTILs density were moderately correlated (r = 0.60), which precluded statistical significance for DFS in a joint model. Three-year DFS and OS in a subgroup of patients with DDIR positivity and T1c/T2N0 disease were 88% and 94%, respectively. CONCLUSION The prognostic role of sTILs and DDIR in early-stage TNBC was confirmed. DDIR signature conferred improved prognosis in two thirds of patients with TNBC treated with adjuvant AC. DDIR signature has the potential to stratify outcome and to identify patients with less projected benefit after AC chemotherapy.
PROTEIN PHOSPHATASE 2A-B′γ Controls Botrytis cinerea Resistance and Developmental Leaf Senescence1[OPEN]

PP2A-B′γ interacts with CALCIUM-DEPENDENT PROTEIN KINASE1 and age-dependently controls salicylic acid-related signaling in plant immunity and developmental leaf senescence. Plants optimize their growth and survival through highly integrated regulatory networks that coordinate defensive measures and developmental transitions in response to environmental cues. Protein phosphatase 2A (PP2A) is a key signaling component that controls stress reactions and growth at different stages of plant development, and the PP2A regulatory subunit PP2A‐B′γ is required for negative regulation of pathogenesis responses and for maintenance of cell homeostasis in short-day conditions. Here, we report molecular mechanisms by which PP2A‐B′γ regulates Botrytis cinerea resistance and leaf senescence in Arabidopsis (Arabidopsis thaliana). We extend the molecular functionality of PP2A‐B′γ to a protein kinase–phosphatase interaction with the defense-associated calcium-dependent protein kinase CPK1 and present indications this interaction may function to control CPK1 activity. In presenescent leaf tissues, PP2A-B′γ is also required to negatively control the expression of salicylic acid-related defense genes, which have recently proven vital in plant resistance to necrotrophic fungal pathogens. In addition, we find the premature leaf yellowing of pp2a-b′γ depends on salicylic acid biosynthesis via SALICYLIC ACID INDUCTION DEFICIENT2 and bears the hallmarks of developmental leaf senescence. We propose PP2A-B′γ age-dependently controls salicylic acid-related signaling in plant immunity and developmental leaf senescence.