Miracle-dz/UniFAR-FTUs huggingface dataset:
Resveratrol counteracts IL‐1β‐mediated impairment of extracellular matrix deposition in 3D articular chondrocyte constructs

When aiming at cell‐based therapies in osteoarthritis (OA), proinflammatory conditions mediated by cytokines such as IL‐1β need to be considered. In recent studies, the phytoalexin resveratrol (RSV) has exhibited potent anti‐inflammatory properties. However, long‐term effects on 3D cartilaginous constructs under inflammatory conditions with regard to tissue quality, especially extracellular matrix (ECM) composition, have remained unexplored. Therefore, we employed long‐term model cultures for cell‐based therapies in an in vitro OA environment and evaluated effects of RSV. Pellet constructs made from expanded porcine articular chondrocytes were cultured with either IL‐1β (1–10 ng/ml) or RSV (50 μM) alone, or a cotreatment with both agents. Treatments were applied for 14 days, either directly after pellet formation or after a preculture period of 7 days. Culture with IL‐1β (10 ng/ml) decreased pellet size and DNA amount and severely compromised glycosaminoglycan (GAG) and collagen content. Cotreatment with RSV distinctly counteracted the proinflammatory catabolism and led to partial rescue of the ECM composition in both culture systems, with especially strong effects on GAG. Marked MMP13 expression was detected in IL‐1β‐treated pellets, but none upon RSV cotreatment. Expression of collagen type I was increased upon IL‐1β treatment and still observed when adding RSV, whereas collagen type X, indicating hypertrophy, was detected exclusively in pellets treated with RSV alone. In conclusion, RSV can counteract IL‐1β‐mediated degradation and distinctly improve cartilaginous ECM deposition in 3D long‐term inflammatory cultures. Nevertheless, potential hypertrophic effects should be taken into account when considering RSV as cotreatment for articular cartilage repair techniques.
How does symbolic success affect redistribution in left-wing voters? A focus on the 2017 French presidential election

Redistribution preferences depend on factors such as self-interest and political views. Recently, Deffains et al. (2016) reported that redistributive behavior is also sensitive to the actual experience of success or failure in a real effort task. While successful participants (‘overachievers’) are more likely to attribute their success to their effort rather than luck and opt for less redistribution, unsuccessful participants (‘underachievers’) tend to attribute their failure to external factors and opt for more redistribution. The aim of the present study was to test how the experience of success (symbolic success) and political views interact in producing redistributive behavior in an experimental setting. The study was conducted during the 2017 French presidential election. Our sample was biased towards left-wing, and most participants reported voting for Mélenchon, Hamon or Macron. Our findings reveal that 1) Macron voters redistribute less than Hamon voters who themselves redistribute less than Mélenchon voters, 2) overachievers redistribute less than underachievers only among Mélenchon voters. This suggests that redistributive behavior is governed primarily by political opinions, and that influence by exogenous manipulation of symbolic success is not homogenous across left-wing political groups.
Association analyses of a genetic variant in long non-coding RNA MEG3 with breast cancer susceptibility and serum MEG3 expression level in the Egyptian population.

BACKGROUND LncRNA MEG3 rs7158663 has been shown to confer cancer susceptibility, maybe through altering its gene expression level. OBJECTIVE We aimed to weigh the effect of rs7158663 on MEG3 serum level and breast cancer susceptibility. METHODS We genotyped rs7158663 G > A and measured serum MEG3 in 150 breast cancer, 95 FA, and 154 controls by the TaqMan method. RESULTS The presence of rs7158663 G > A is a risk factor for breast cancer among fibroadenoma patients and controls, AA vs. GG genotypes (OR = 6.320, 95% CI = 2.587-15.439, P< 0.0001 when compared to controls and OR = 10.825, 95% CI = 1.929-60.742, P= 0.007 when compared to fibroadenoma). Decreased serum MEG3 was observed in breast cancer group when compared with fibroadenoma and/or controls [median (IQR) = 0.43 (0.27-0.55)] (P< 0.0001). However, increased serum MEG3 was noted in fibroadenoma group when compared with controls (P< 0.0001). A significance decreased serum MEG3 was found to be associated with mutant A allele than with wild G allele (P> 0.0001). The results showed that rs7158663 and lower MEG3 were significantly associated with patients with higher TNM staging and larger tumor size > 5 cm. CONCLUSION The presence of both rs7158663 and low MEG3 are diagnostic and unfavorable prognostic factors for BC patients.
Clinicopathological findings of a long-term survivor of V180I genetic Creutzfeldt-Jakob disease

ABSTRACT The clinical characteristics of genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation in the PRNP gene (V180I gCJD) are unique: elderly-onset, gradual progression, sporadic fashion, and cortical oedematous hyper-intensity on diffusion-weighted MRI (DW-MRI). This phenotype may become a potential target of future clinical therapeutic trials. The average disease duration of V180I gCJD patients is 23–27 months; however, considerably long-term survivors are also reported. The factors influencing survival and the clinicopathological characteristics of long-term survivors remain unknown. Herein, we report clinicopathological findings of a long-term survivor of V180I gCJD. A 78-year old woman was admitted to our hospital due to dementia and left hand tremor approximately 1.5 months after symptom onset. Neurological examination revealed dementia, frontal signs, and left hand tremor at admission. She had no family history of dementia or other neurological disease. DW-MRI revealed cortical oedematous hyper-intensities in the bilateral frontal lobes and the right temporal and parietal lobes. PRNP gene analysis indicated a V180I mutation with methionine homozygosity at codon 129. The symptoms gradually progressed, and she died of aspiration pneumonia 61 months after symptom onset. Neuropathological examination revealed severe cerebral atrophy with moderate to severe gliosis, but the brainstem was well preserved. Various-sized and non-confluent vacuole type spongiform changes were extensively observed in the cerebral cortices. Prion protein (PrP) immunostaining revealed weak and synaptic-type PrP deposits in the cerebral cortices. We consider that long-term tube feeding, and very mild brainstem involvement may be associated with the long-term survival of our V180I gCJD patient.
Human Copper-Containing Amine Oxidases in Drug Design and Development

Two members of the copper-containing amine oxidase family are physiologically important proteins: (1) Diamine oxidase (hDAO; AOC1) with a preference for diamines is involved in degradation of histamine and (2) Vascular adhesion protein-1 (hVAP-1; AOC3) with a preference for monoamines is a multifunctional cell-surface receptor and an enzyme. hVAP-1-targeted inhibitors are designed to treat inflammatory diseases and cancer, whereas the off-target binding of the designed inhibitors to hDAO might result in adverse drug reactions. The X-ray structures for both human enzymes are solved and provide the basis for computer-aided inhibitor design, which has been reported by several research groups. Although the putative off-target effect of hDAO is less studied, computational methods could be easily utilized to avoid the binding of VAP-1-targeted inhibitors to hDAO. The choice of the model organism for preclinical testing of hVAP-1 inhibitors is not either trivial due to species-specific binding properties of designed inhibitors and different repertoire of copper-containing amine oxidase family members in mammalian species. Thus, the facts that should be considered in hVAP-1-targeted inhibitor design are discussed in light of the applied structural bioinformatics and structural biology approaches.
Peripheral insulin administration enhances the electrical activity of oxytocin and vasopressin neurones in vivo

Oxytocin neurones are involved in the regulation of energy balance through diverse central and peripheral actions and, in rats, they are potently activated by gavage of sweet substances. Here, we test the hypothesis that this activation is mediated by the central actions of insulin. We show that, in urethane‐anaesthetised rats, oxytocin cells in the supraoptic nucleus show prolonged activation after i.v. injections of insulin, and that this response is greater in fasted rats than in non‐fasted rats. Vasopressin cells are also activated, although less consistently. We also show that this activation of oxytocin cells is independent of changes in plasma glucose concentration, and is completely blocked by central (i.c.v.) administration of an insulin receptor antagonist. Finally, we replicate the previously published finding that oxytocin cells are activated by gavage of sweetened condensed milk, and show that this response too is completely blocked by central administration of an insulin receptor antagonist. We conclude that the response of oxytocin cells to gavage of sweetened condensed milk is mediated by the central actions of insulin.
Computer simulations explain mutation-induced effects on the DNA editing by adenine base editors

We uncovered structural and functional changes induced by mutations that dictate the DNA editing activity of ABE enzymes. Adenine base editors, which were developed by engineering a transfer RNA adenosine deaminase enzyme (TadA) into a DNA editing enzyme (TadA*), enable precise modification of A:T to G⋮C base pairs. Here, we use molecular dynamics simulations to uncover the structural and functional roles played by the initial mutations in the onset of the DNA editing activity by TadA*. Atomistic insights reveal that early mutations lead to intricate conformational changes in the structure of TadA*. In particular, the first mutation, Asp108Asn, induces an enhancement in the binding affinity of TadA to DNA. In silico and in vivo reversion analyses verify the importance of this single mutation in imparting functional promiscuity to TadA* and demonstrate that TadA* performs DNA base editing as a monomer rather than a dimer.
Half-precessional cycle of thermocline temperature in the western equatorial Pacific and its bihemispheric dynamics

Significance The precessional insolation plays a critical role in modulating the low-latitude oceanographic changes through ENSO-like dynamics. While previous studies focused on the precessional insolation-induced low-latitude surface water changes, our well-dated, centennial-resolution proxy data and numerical simulation reveal the half-precession cycle of thermocline water temperature (TWT) in the western equatorial Pacific that directly linked to ENSO-like zonal temperature seesaw over the equatorial Pacific. These half-precessional TWT changes are proposed to originate from the interplay of subtropical-to-tropical thermocline anomalies forced by the antiphased meridional insolation gradients in the two hemispheres at the precessional band. This work illustrates that the tropical thermocline water could bridge the meridional climatic processes and the east−west ENSO-like dynamics at orbital timescales. The El Niño−Southern Oscillation (ENSO), which is tightly coupled to the equatorial thermocline in the Pacific, is the dominant source of interannual climate variability, but its long-term evolution in response to climate change remains highly uncertain. This study uses Mg/Ca in planktonic foraminiferal shells to reconstruct sea surface and thermocline water temperatures (SST and TWT) for the past 142 ky in a western equatorial Pacific (WEP) core MD01-2386. Unlike the dominant 100-ky glacial−interglacial cycle recorded by SST and δ18O, which echoes the pattern seen in other WEP sites, the upper ocean thermal gradient shows a clear half-precessional (9.4 ky or 12.7 ky) cycle as indicated by the reconstructed and simulated temperature (ΔT) and δ18O differences between the surface and thermocline waters. This phenomenon is attributed to the interplay of subtropical-to-tropical thermocline anomalies forced by the antiphased meridional insolation gradients in the two hemispheres at the precessional band. In particular, the TWT shows greater variability than SST, and dominates the ΔT changes which couple with the west−east SST difference in the equatorial Pacific at the half-precessional band, implying a decisive role of the tropical thermocline in orbital-scale climate change.
Safety update of etanercept treatment for moderate to severe plaque psoriasis

ABSTRACT Introduction: Conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) for patients with psoriasis are often linked to inadequate outcomes and risk of multiple adverse effects. Biologic agents such as etanercept (ETN) have revolutionized the therapeutic management of psoriasis, allowing the treatment of most difficult cases, and fragile patients. Areas covered: The authors searched PubMed using the term ‘psoriasis,’ ‘etanercept,’ and ‘safety. ’ Articles considered by the authors to be most relevant, such as randomized controlled studies, cohort studies, and review articles placing emphasis on studies of efficacy and safety were selected. Case reports and letters relating to safety were also included. The main sources of data referenced by these articles were also included in the review. Besides, to get the relevant studies, the reference lists were examined to identify the potentially available studies. The aim of this review is to describe the safety profile of ETN, used for psoriasis treatment, focusing on related clinical implications. Expert opinion: ETN has a favorable safety profile, and its use should be largely considered in psoriatic patients. Caution should be recommended in case of chronic heart failure, autoimmune disease, previous malignancies, familial history of demyelinating diseases, latent TBC infection, chronic HBV and HCV infection or HIV.
Mind the gap between feeling bad and feeling dead: Stress but not death reminders elicit endocrine responses

Abstract Stressors and mortality salience share considerable conceptual overlap. Thus, we examined the impact of a standard mortality salience and a standard stress manipulation on the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis via endocrine measures of stress; a neutral control condition completed the design. The results revealed that stress elicits increased salivary α-amylase and salivary cortisol reactions; however, no endocrine reactions were found in the mortality salience and the control conditions. To the contrary, we did not find any differences regarding positive and negative affect between any conditions. Implications for social and health psychology are being discussed.
Better cognitive efficiency is associated with increased experimental anxiety.

There is increased interest in the development of cognitive training targeting working memory (WM) to alleviate anxiety symptoms, but the effectiveness of such an approach is unclear. Improved understanding of the effect of cognitive training on anxiety may facilitate the development of more effective cognitive training treatment for anxiety disorders. This study uses an experimental approach to examine the interplay of WM and anxiety following WM training. Previous studies show that increased demand on WM reduces concurrent anxiety evoked by threat of shock (induced anxiety). However, improving WM pharmacologically or via exercise prevents this anxiolytic effect. Conceivably, improving WM frees up cognitive resources to process threat information, thereby increasing anxiety. The present study tested the hypothesis that practicing a high load WM (i.e., increased demand) task would improve WM, and thus, free cognitive resources to process threat of shock, resulting in more anxiety (i.e., greater startle) during a subsequent WM task. Participants were randomly assigned to two training groups. The active-training group (N = 20) was trained on a 1- (low load) & 3-back (high load) WM task, whereas the control-training group (N = 20) performed a 0-back WM task. The experimental phase, similar in both groups, consisted of a 1- & 3-back WM task performed during both threat of shock and safety. As predicted, active training improved WM accuracy and increased anxiety during the experimental 3-back WM task. Therefore, improving WM efficiency can increase anxiety, possibly by freeing WM resources to process threat information.
Changes in starch structures and in vitro digestion characteristics during maize (Zea mays L.) germination

Abstract This study analyzed changes in the starch structures and in vitro digestion profiles of a specific maize cultivar, Jike 728 (JK728), in Jilin, China, after 0–5 days of germination. The total starch, amylose, and amylopectin contents decreased significantly during germination. The average molecular weight of the starch compounds also decreased significantly during germination. The proportion of amylopectin with a degree of polymerization (DP) of 13–24 significantly decreased, while the relative abundance of amylopectin with DP values of 6–12, 25–36, and 37–60 significantly increased. The X‐ray diffraction (XRD) patterns of all samples were characteristic of A‐type starch, and the starch relative crystallinity decreased over time. The proportions of slowly digestible starch and resistant starch decreased significantly, while the proportion of rapidly digestible starch increased significantly during germination. Germination is an easy, inexpensive, and low‐carbon processing method. This study indicates that germination is an effective way to control the physical properties and digestibility of starch in maize. The changes observed in the physical properties and digestibility of maize starch after germination provide scientists with a platform to understand starch modification mechanisms that might have potential applications on an industrial scale.
Contrasting acclimation responses to elevated CO2 and warming between an evergreen and a deciduous boreal conifer

Rising atmospheric carbon dioxide (CO2) concentrations may warm northern latitudes up to 8°C by the end of the century. Boreal forests play a large role in the global carbon cycle, and the responses of northern trees to climate change will thus impact the trajectory of future CO2 increases. We grew two North American boreal tree species at a range of future climate conditions to assess how growth and carbon fluxes were altered by high CO2 and warming. Black spruce (Picea mariana, an evergreen conifer) and tamarack (Larix laricina, a deciduous conifer) were grown under ambient (407 ppm) or elevated CO2 (750 ppm) and either ambient temperatures, a 4°C warming, or an 8°C warming. In both species, the thermal optimum of net photosynthesis (ToptA) increased and maximum photosynthetic rates declined in warm‐grown seedlings, but the strength of these changes varied between species. Photosynthetic capacity (maximum rates of Rubisco carboxylation, Vcmax, and of electron transport, Jmax) was reduced in warm‐grown seedlings, correlating with reductions in leaf N and chlorophyll concentrations. Warming increased the activation energy for Vcmax and Jmax (EaV and EaJ, respectively) and the thermal optimum for Jmax. In both species, the ToptA was positively correlated with both EaV and EaJ, but negatively correlated with the ratio of Jmax/Vcmax. Respiration acclimated to elevated temperatures, but there were no treatment effects on the Q10 of respiration (the increase in respiration for a 10°C increase in leaf temperature). A warming of 4°C increased biomass in tamarack, while warming reduced biomass in spruce. We show that climate change is likely to negatively affect photosynthesis and growth in black spruce more than in tamarack, and that parameters used to model photosynthesis in dynamic global vegetation models (EaV and EaJ) show no response to elevated CO2.
INCIDENCE, RISK FACTORS, AND CLINICAL IMPLICATIONS OF DELAYED HYPOPARATHYROIDISM ON POSTOPERATIVE DAY TWO FOLLOWING TOTAL THYROIDECTOMY FOR PAPILLARY THYROID CARCINOMA.

Objective This study aimed to investigate the incidence rates, risk factors, and clinical implications of delayed hypoparathyroidism on postoperative day two (POD-2) after total thyroidectomy in patients with papillary thyroid carcinoma. Methods This study included 410 patients with normal serum intact parathyroid hormone (iPTH) and calcium levels on POD-1 who were classified into two groups according to the presence or absence of delayed hypoparathyroidism on POD-2. Results Of the 410 patients, 98 experienced delayed hypoparathyroidism on POD-2 (23.9%). The significant risk factors for delayed hypoparathyroidism on POD-2 included female gender, age older than 45 years, central lymph node dissection, increased number of excised lymph nodes, and low POD-1 versus preoperative iPTH ratios. Additionally, delayed hypoparathyroidism on POD-2 was found to be a significant risk factor for hypocalcemia on POD-2 and permanent hypoparathyroidism. Conclusion Prophylactic calcium supplementation and long-term surveillance for permanent hypoparathyroidism should be considered in patients with risk factors for delayed hypoparathyroidism on POD-2.
Clinical Characteristics and Postoperative Outcomes of Patients Presenting With Upper Gastrointestinal Tract Crohn Disease

Purpose Upper gastrointestinal (GI) tract involvement in Crohn disease (CD) is rare and effectiveness of surgical treatment is limited. The aim of this study was to evaluate characteristics and surgical outcomes of upper GI CD. Methods Medical records of 811 patients who underwent intestinal surgery for CD between January 2006 and December 2015 at a single institution were reviewed. Upper GI CD was defined by involvement of the stomach to the fourth portion of duodenum, with or without concomitant small/large bowel CD involvement according to a modification of the Montreal classification. Results We identified 24 patients (21 males, 3 females) who underwent surgery for upper GI CD. The mean age at diagnosis was 27 ± 12 years, the mean age at surgery was 33 ± 11 years, and the mean duration of CD was 73.6 ± 56.6 months. Fifteen patients (62.5%) had history of previous perianal surgery. Ten patients (41.7%) had duodenal or gastric stricture and 14 patients (58.3%) had penetrating fistula; patients with fistula were significantly more likely to develop complications (57.1% vs. 20.0%, P = 0.035). One patient with stricture had surgical recurrence. In seven patients with fistula, fistula was related to previous anastomosis. Patients with fistula had significantly longer hospital stays than those with stricture (16 days vs. 11 days, P = 0.01). Conclusion Upper GI CD is rare among CD types (2.96%). In patients with upper GI CD, penetrating fistula was associated with longer hospital stay and more complications.