Miracle-dz/UniFAR-FTUs huggingface dataset:
TLR7 agonist modulation of post-asphyxial neurophysiological and cardiovascular adaptations in preterm fetal sheep.

Activation of toll-like receptors (TLRs) after hypoxic-ischemic brain injury can both exacerbate injury, but also alleviate cell loss as recently demonstrated with the TLR7 agonist Gardiquimod (GDQ). However, TLR agonists also modulate vascular function and neuronal excitability. Thus, we examined the effects of TLR7 activation with GDQ on cardiovascular function and seizures after asphyxia in preterm fetal sheep at 0.7 gestation (104 days, term ~147 days). Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion for 25 minutes, or asphyxia followed by a continuous intracerebroventricular infusion of 3.34 mg of GDQ from 1-4 hours after asphyxia. Fetuses were monitored continuously for 72 hours post-asphyxia. GDQ treatment was associated with sustained, moderate hypertension for 72 hours (P<0.05), with a transient increase in heart rate. Electroencephalographic (EEG) power was suppressed for the entire post-asphyxial period in both groups, whereas EEG spectral edge transiently increased during the GDQ infusion compared with asphyxia alone (P<0.05), with higher beta and lower delta EEG frequencies (P<0.05). This increase in EEG frequency was not related to epileptiform activity. Following the GDQ infusion there was earlier onset of high amplitude stereotypic evolving seizures, with increased numbers of seizures and seizure burden (P<0.05). Hemodynamic function and seizure activity are important indices of preterm wellbeing. These data highlight the importance of physiological monitoring during preclinical testing of potential neuroprotective strategies.
NBR1‐mediated p62‐liquid droplets enhance the Keap1‐Nrf2 system

p62/SQSTM1 is a multivalent protein that has the ability to cause liquid–liquid phase separation and serves as a receptor protein that participates in cargo isolation during selective autophagy. This protein is also involved in the non‐canonical activation of the Keap1‐Nrf2 system, a major oxidative stress response pathway. Here, we show a role of neighbor of BRCA1 gene 1 (NBR1), an autophagy receptor structurally similar to p62/SQSTM1, in p62‐liquid droplet formation and Keap1‐Nrf2 pathway activation. Overexpression of NBR1 blocks selective degradation of p62/SQSTM1 through autophagy and promotes the accumulation and phosphorylation of p62/SQSTM1 in liquid‐like bodies, which is required for the activation of Nrf2. NBR1 is induced in response to oxidative stress, which triggers p62‐mediated Nrf2 activation. Conversely, loss of Nbr1 suppresses not only the formation of p62/SQSTM1‐liquid droplets, but also of p62‐dependent Nrf2 activation during oxidative stress. Taken together, our results show that NBR1 mediates p62/SQSTM1‐liquid droplet formation to activate the Keap1‐Nrf2 pathway.
Post‐natal co‐development of the microbiota and gut barrier function follows different paths in the small and large intestine in piglets

Gut microbiota and intestinal barrier co‐develop after birth, establishing a homeostatic state whereby mucosal cells cohabit with commensal bacteria. We hypothesized that this post‐natal co‐development follows different timings depending on the intestinal site considered. Jejunal, ileal, and colonic luminal contents and mucosa were sampled in suckling piglets at post‐natal day (PND) 0, 2, 7, 14, and 28. Jejunal, ileal, and colonic luminal microbiota (evaluated by 16S DNA sequencing followed by beta‐diversity analysis) clustered at PND2 but colonic microbiota diverge afterwards (P < .05). Mucosal permeability, evaluated in Ussing chambers, increased with age in the jejunum and ileum (P < .05) but not the colon. Expression of pattern recognition receptor (PRR) exhibited different patterns (gradual or sharp increase, decrease, or no change with age, P < .05) depending on PRR and intestinal site considered. Principal component analysis of mucosa data revealed clear clustering of colonic samples, irrespective of the age and clustering of jejunal and ileal samples, with gradual changes with age. Correlation analysis highlighted three families correlating with mucosal parameters: Enterobacteriaceae in the jejunum, Peptostreptococcaceae in the ileum, and Micrococcaceae in the colon. In conclusion, small and large intestine display close microbiota composition early in life but distinct mucosal phenotype and follow very different post‐natal development.
Preliminary evaluation of an osteochondral autograft, a prosthetic implant, and a biphasic absorbable implant for osteochondral reconstruction in a sheep model

Abstract Objective To determine the ability of three implants to enhance the healing of osteochondral defects: (1) a biphasic construct composed of calcium phosphate (CaP) and chitosan/cellulosic polymer, (2) a titanium‐polyurethane implant, and (3) an osteochondral autograft. Study design Experimental study. Animals Ten adult female sheep. Methods In five sheep, an 8‐mm diameter osteochondral defect was created on the medial femoral condyle of a stifle and filled with a synthetic titanium‐polyurethane implant. In five sheep, a similar defect was filled with an osteochondral autograft, and the donor site was filled with a biphasic construct combining CaP granules and a chitosan/cellulosic polymer. Sheep were monitored daily for lameness. Stifle radiographs and MRI were evaluated at 20 weeks, prior to animals being humanely killed. Surgical sites were evaluated with histology, microcomputed tomography, and scanning electron microscopy. Results Clinical outcomes were satisfactory regardless of the tested biomaterials. All implants appeared in place on imaging studies. Osteointegration of prosthetic implants varied between sites, with limited ingrowth of new bone into the titanium structure. Autografts and biphasic constructs were consistently well integrated in subchondral bone. All autografts except one contained a cartilage surface, and all biphasic constructs except one partially restored hyaline cartilage surface. Conclusion Biphasic constructs supported hyaline cartilage and subchondral bone regeneration, although restoration of the articular cartilage was incomplete. Clinical impact Biphasic constructs may provide an alternative treatment for osteochondral defects, offering a less invasive approach compared with autologous grafts and eliminating the requirement for a prosthetic implant.
Effectiveness of percutaneous cement injection on proximal junctional failure after posterior lumbar interbody fusion

Abstract Proximal junctional failure (PJF) is the greatest challenge after posterior lumbar interbody fusion (PLIF). The aim of this study was to evaluate the effectiveness of percutaneous cement injection (PCI) for PJF after PLIF patients requiring surgical revision. In this retrospective clinical study, we reviewed 7 patients requiring surgical revision for PJF after PLIF with 18 months follow-up. They received PCI at the collapsed vertebral body and supra-adjacent vertebra, with or without intervertebral disc intervention. The outcome measures were radiographic findings and revision surgery. Two different radiographic parameters (wedging rate (%) of the fractured vertebral body and local kyphosis angle) were used, and were performed before and immediately after PCI, and 18 month after the PCI. In our study, we showed that 5 of 7 patients who experienced PJF after PLIF did not receive any revision surgery after PCI. Immediately after cement injection, the anterior wedging rate (%) and the local kyphosis angle were significantly improved (P = .018, P = .028). The anterior wedging rates (%) and local kyphosis angle, at pre-PCI, immediate after PCI, and at final follow-up, were not significantly different between the non-revision surgery and revision surgery groups. Five of 7 patients who experienced PJF after PLIF did not receive revision surgery after PCI. Considering that general anesthesia and open surgery are high-risk procedures for geriatric patients, our results suggest that non-surgical PCI could be a viable alternative treatment option for PJF. SMC2017-01-011-001. Retrospectively registered 18 January 2017.
Phellinus linteus polysaccharide extract improves insulin resistance by regulating gut microbiota composition

The hypoglycemic effect of Phellinus linteus polysaccharide extract (PLPE) has been documented in several previous studies, but the functional interactions among PLPE, gut microbiota, and the hypoglycemic effect remain unclear. We examined the regulatory effect of PLPE on gut microbiota, and the molecular mechanism underlying improvement of insulin resistance, using a type 2 diabetic rat model. Here, 24 male Sprague‐Dawley rats were randomly divided into four groups that were subjected to intervention of saline (normal and model control group), metformin (120 mg/kg.bw), and PLPE (600 mg/kg.bw) by oral administration. After 8 weeks of treatment, PLPE increased levels of short‐chain fatty acids (SCFAs) by enhancing abundance of SCFA‐producing bacteria. SCFAs maintained intestinal barrier function and reduced lipopolysaccharides content in blood, thereby helping to reduce systemic inflammation and reverse insulin resistance. Our findings suggest that PLPE (in which polysaccharides are the major component) has potential application as a prebiotic for regulating gut microbiota composition in diabetic patients.
Foreign objects in college bodies: young women’s feelings about long-acting reversible contraception (LARC)

ABSTRACT Long-acting reversible contraceptives (LARC) are now recommended for use among nulliparous young women to prevent unintended pregnancy. While research has explored LARC knowledge, attitudes, and use among young women in the United States, college women’s feelings about LARC have received limited attention. This article reports findings from a focus group study conducted with a convenience sample of 45 women, ages 18–25 years, enrolled in a large public university in the southeastern USA in April 2017. Focus groups combined LARC users and non-users and elicited a range of positive and negative affective responses to LARC. Some participants had an aversion to LARC because they perceived them to be unnatural, while others felt a sense of security because of their long-term effectiveness. Feelings about the location and mode of insertion for the intrauterine device (IUD) versus the implant played a significant role in the decision to use a specific LARC method: some found being able to feel the implant in their arm reassuring, while others found it disturbing and preferred the IUD. College-going LARC users also appear to be effective advocates for LARC use among their peers.
Wood Dust Exposure and Risk of Sinonasal and Nasopharyngeal Cancer: A Meta-Analysis

Objectives: In order to examine association between wood dust exposure and sin nasal and nasopharyngeal cancer. Methods: We performed a systematic search of the literature. Both random and fixed effects were used to calculate odd ratios (ORs) and 95% confidence intervals (95%CIs) of each study. Results: A significant increased risk of sinonasal and nasopharyngeal cancer was associated with wood dust exposure. The ORs for sinonasal cancer were 7.78 (CI: 2.97-20.25) among adenocarcinoma studies and 1.18 (CI: 0.642.19) among squalors cell carcinoma studies. Contrary to women (OR=2.11, CI: 0.71-6.32), an elevated risk of sinonasal cancer was observed among men (OR=2.29, CI: 1.55-3.41). The OR for nasopharyngeal cancer was 1.87 (CI: 1.57-2.38). Conclusion: Wood dust exposure was a high risk associated with sinosnasal and nasopharyngeal cancer. Except for female and squalors cell carcinoma studies in sinosnasal cancer, all stratifications in our meta-analysis present a significant risk between sinosnasal or nasopharyngeal cancer and wood dust exposure.
Colour discrimination among patients with schizophrenia in Lebanon

Abstract Background: Abnormalities and contrast sensitivity have already been studied in schizophrenia. However, the relationship between symptom severity in schizophrenia and colour vision sensitivity has not been studied systematically. Aim: Our objective was to evaluate colour discrimination in patients with schizophrenia compared to controls and examine if this colour discrimination is correlated with schizophrenia symptoms’ severity. Methods: This case–control study, performed between January and April 2017, included 50 schizophrenic patients and 50 healthy controls matched for age and sex. The Positive and Negative Symptoms Scale (PANSS) was used to determine the schizophrenia symptoms’ severity. Colour discrimination was evaluated using the total error score (TES) generated using the Farnsworth D-15 test. The higher the TES, the more severe colourblindness. Results: A significantly higher mean TES was found in schizophrenics (30.32) compared to healthy patients (13.07) (p < 0.001). Colour blindness was correlated to the severity of schizophrenic symptoms only in the subgroup of patients with severe schizophrenia. Conclusion: Colour vision defect is a common feature in schizophrenia, and may be more significant when related to psychotic symptoms. KEY POINTS A significantly higher mean TES was found in schizophrenics compared to healthy patients. Colour blindness was correlated to the severity of schizophrenic symptoms only in the subgroup of patients with severe schizophrenia. Colour vision defect is a common feature in schizophrenia, and may be more significant when related to psychotic symptoms.
An in vivo study of the impact of deficiency in the DNA repair proteins PAXX and XLF on development and maturation of the hemolymphoid system

Repair of DNA double-strand breaks by the nonhomologous end joining pathway is central for proper development of the adaptive immune system. This repair pathway involves eight factors, including XRCC4-like factor (XLF)/Cernunnos and the paralog of XRCC4 and XLF, PAXX nonhomologous end joining factor (PAXX). Xlf−/− and Paxx−/− mice are viable and exhibit only a mild immunophenotype. However, mice lacking both PAXX and XLF are embryonic lethal because postmitotic neurons undergo massive apoptosis in embryos. To decipher the roles of PAXX and XLF in both variable, diversity, and joining recombination and immunoglobulin class switch recombination, here, using Cre/lox-specific deletion to prevent double-KO embryonic lethality, we developed two mouse models of a conditional Xlf KO in a Paxx−/− background. Cre expressed under control of the iVav or CD21 promoter enabled Xlf deletion in early hematopoietic progenitors and splenic mature B cells, respectively. We demonstrate the XLF and PAXX interplay during variable, diversity, and joining recombination in vivo but not during class switch recombination, for which PAXX appeared to be fully dispensable. Xlf/Paxx double KO in hematopoietic progenitors resulted in a shorter lifespan associated with onset of thymic lymphomas, revealing a genome caretaking function of XLF/PAXX.
High-intensity cycling re-warm up within a very short time-frame increases the subsequent intermittent sprint performance

Abstract This study investigated the effect of high-intensity cycling re-warm up (RW) within a very short time-frame on the subsequent intermittent sprint performance. Twelve active males completed three trials in random order: control (CON); 3-min RW at 30% of maximal oxygen uptake (VO2max) (RW30); and 1-min RW at 90% of VO2max (RW90). During the experimental trials, participants performed 40-min intermittent cycling exercise followed by 15-min rest. During the rest period, participants completed CON, RW30, or RW90. After the rest period, participants performed the Cycling Intermittent-Sprint Protocol (CISP), which consisted of 10-s rest, 5-s maximal sprint, and 105-s active recovery with the cycles repeated over 10 min. The mean work during sprint for the CISP was significantly higher in both RW trials than in the CON trial (mean±standard deviation; CON: 3539±698 J; RW30: 3724±720 J; RW90: 3739±736 J; p<0.05). The mean electromyogram amplitude during the sprint for the CISP was higher in the RW30 trial than in the CON trial; however, there was no significant difference between the two trials (p=0.06). The mean median frequency during sprint for the CISP was significantly higher in the RW90 trial than in the other trials (p<0.05). Rectal temperature did not differ among the three trials. Oxygenated haemoglobin during the initial 30 s of the CISP was significantly higher in the RW90 trial than in the CON trial (p<0.05). Compared with seated rest, RW, irrespective of whether it comprised 1-min at 90% of VO2max or 3-min at 30% of VO2max, increased the subsequent intermittent sprint performance.
Survival analysis of patients with glioblastoma treated by long-term administration of temozolomide

Abstract This analysis aimed to investigate whether the long-term administration of temozolomide (TMZ) claimed a survival advantage for patients with glioblastoma in China. A total of 75 patients with newly diagnosed glioblastoma at the Department of Radiation Oncology, Shenzhen People's Hospital between August 2008 and August 2016 were retrospectively evaluated during analysis. A propensity-matched analysis was performed to balance the basic characteristics of patients between compared groups. Kaplan–Meier method and Cox proportional hazards model were used to assess progression-free survival (PFS) and overall survival (OS) of patients receiving 6 adjuvant TMZ cycles compared with patients treated with more than 6 cycles. Twenty of 75 patients received more than 6 cycles of TMZ, and the other 55 patients were treated with a median of 6 cycles ranging from 1 to 6. The patients with long-term administration of TMZ had better OS (47.0 months, 95% CI 20.0–73.9 vs 20.6 months, 95% CI 17.9–23.2, P = .014) but not PFS (17.0 months, 95% CI 10.1–24.5 vs 14.2 months, 95% CI 11.8–16.6, P = .133). Balancing the clinical factors with a propensity-matched analysis also showed the significant advantage of prolonged TMZ application in terms of OS but not PFS. Prolonged administration of TMZ beyond 6 cycles did demonstrate survival benefits for patients with initially diagnosed glioblastoma.
Incidence of hospital-acquired pressure ulcers in patients with "minimal risk" according to the "Norton-MI" scale

Introduction Pressure ulcers (PUs) nowadays are a major health problem in society, associated with increased morbidity and increased health care costs. The incidence of HAPU is an indicator of health care quality. Objective To describe the profile of patients with minimal risk on the Norton-MI scale who developed PUs during hospitalization, and to identify the incidence of hospital-acquired pressure ulcers (HAPU). Methods Retrospective cohort study conducted between 2014 and 2017. Study population Patients over 18 years of age classified as "minimum risk" according to Norton-MI, admitted to acute hospital units of the Severo Ochoa University Hospital—Madrid-Spain. Patients were classified as patients with hospital-acquired pressure ulcers (PWHAPU) if they developed one or more new PU during their hospitalization. Variables Sociodemographic variables, hospitalization units, Morton-MI score and characteristics of the risk factors of HAPU were studied. Results The risk of PU was evaluated in 5530 patients, being 1260 patients classified as "minimum risk", with a median of 16 points in the Norton-MI scale. The average age was 76 years old and 52.5% were women. Principal causes of admission: traumatological pathologies (20.8%) and cardiovascular pathologies (20%). 129 HAPU were diagnosed in 112 patients, implying an incidence of HAPU of 8.89% (CI95%: 7.44–10.59). 106 PWHAPU (94.6%) presented up to 6 risk factors. The excess pressure and altered skin sensibility were identified as statistically significant risk factors as predictive factors of HAPU. In terms of severity, 55% of the HAPU were category I and 42.6% were category II, mainly with anatomical sacro-coxygeal location. In 65.2% of the patients the HAPU appeared in the first week of hospitalization. Conclusion In our study the incidence of HAPU in patients classified as minimum risk with Norton-MI scale was 8.89%. This elevated risk suggests for future investigations to develop new validity studies of the Norton-MI scale and to maintain a continuo training of professionals in the knowledge of PU risk assessment scales for their safe application in the patients, since it directs the practice of care in the prevention of PUs. It would be advisable to specially control the risk of PUs in care units, mainly in the first week of their hospital stay to minimize the HAPU incidence.
Analysis of the laboratory indexes and risk factors in 189 cases of severe fever with thrombocytopenia syndrome

Abstract The current study aimed to analyze the clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) and to explore the risk factors of critical patients. From 2016 to 2018, we collected the hospitalized diagnosed cases with SFTS in Jinan infectious disease hospital of Shandong University and analyzed by the descriptive epidemiological method. According to the prognosis, they were divided into general group and severe group. The epidemiological characteristics, clinical features, and laboratory indexes of these 2 groups of patients were compared and analyzed at the first visit. The risk factors related to the severity of the disease were analyzed by univariate Logistic regression. In total, 189 cases of SFTS were treated during the period and 33 deaths occurred in the severe group, with the fatality rate of 17.46%. The patients’ age (χ2 = 8.864, P < .01), ALT (Z = −2.304, P = .03), AST (Z = −3.361, P < .01), GLU (t = −4.115, P < .01), CK (Z = −3.964, P < .01), CK-MB (Z = −2.225, P = .03), LDH (Z = −3.655, P < .01), α-HBDH (Z = −2.040, P = .04), APTT (t = −3.355, P < .01), BUN (Z = −2.040, P = .04), Cr (Z = −3.071, P = .01), and D-dimer (Z = −2.026, P = .04) in the severe group were higher than that in the normal group, but the blood platelet (PLT) counts were significantly lower (Z = −2.778, P < .01) than that in the normal group. With the neuropsychiatric symptoms (OR = 24.083, 95% CI = 6.064–95.642), skin bleeding point (OR = 30.000, 95% CI = 6.936–129.764), multiple organ dysfunction (OR = 34.048, 95% CI = 7.740–149.782), past medical history (OR = 3.792, 95% CI = 1.284–11.200), and fasting glucose elevation (OR = 1.359, 95% CI = 1.106–1.668) could predict the severity of the SFTS. In summary, the abnormality of the laboratory index, the special clinical manifestations, and the past medical history of SFTS patients were the important basis for judging the patient's serious condition.