Miracle-dz/UniFAR-FTUs huggingface dataset:
Family structure and alcohol use disorder: A register-based cohort study among offspring with and without parental alcohol use disorder.

AIMS To assess whether parental alcohol use disorder (AUD) is associated with higher risks of living in a non-intact family and assess whether non-intact family structure is associated with higher risks of AUD in the offspring. DESIGN Prospective cohort study. SETTING Danish nationwide registries. PARTICIPANTS 9,948 parental AUD offspring and 98,136 reference offspring from the Danish population. MEASUREMENTS Family structure assessed at birth and at each birthday until age 15 as intact or non-intact (with mother only, father only or neither parent). Years lived in an intact family defined as total number of years lived with both parents from birth until 15th birthday. AUD defined as registration in medical, treatment and cause of death registries. Data was analyzed by Cox regression. FINDINGS At birth, 30.9% (95% CI = 29.1-32.6) of parental AUD offspring and 10.7% (95% CI = 10.3-11.0) of reference offspring lived in a non-intact family. At age 15, the numbers were 84.6% (95% CI = 83.9-85.3) and 38.4% (95% CI = 38.1-38.7). Parental AUD was associated with a higher risk of offspring AUD (HR = 1.88, 95% CI = 1.74-2.02). Offspring were at lower risk of AUD if they lived 15 years in an intact family compared with offspring who never lived in an intact family (HR = 0.67, 95% CI = 0.52-0.87 for those with parental AUD, and HR = 0.53, 95% CI = 0.48-0.59 for those whose parents did not have AUD). Findings were inconclusive as to whether or not an association was present between family structure and AUD among offspring with parental AUD and reference offspring. CONCLUSIONS The prevalence of non-intact family structure appears to be higher in offspring of parents with alcohol use disorder (AUD) than among offspring from the general population. Parental AUD appears to be associated with increased risk of offspring AUD, and non-intact family structure appears to be associated with increased risk of offspring AUD regardless of parental AUD.
Combination of microfluidic chip and electrostatic atomization for the preparation of drug-loaded core–shell nanoparticles

To overcome the shortcoming of drug-loaded nanoparticles, such as high initial burst release and wide size distribution, a novel manufacturing technique for core–shell structure nanoparticle was developed by combining microfluidic chip and electrohydrodynamic atomization. In this study, the mixture solution of the surfactant 1, 2- dipalmitoyl-sn-glycero-3-phosphoglycerol and the polymeric coating material polylactic-glycolic-acid was introduced into the outer microchannel of the microfluidic chip as the particle’s shell. And the encapsulated drug paclitaxel was pumped into the inner microchannel as the core. Then, the particles with a nanoscale-size core–shell structure were generated by applying an electric field on the laminar flow which was formed in the microfluidic chip. Operation parameters, including working voltage, carrier material and surfactant concentration as well as liquid flow rates were optimized for nanoparticles generation. The properties of drug-loaded nanoparticles in terms of their particle size, zeta potential and encapsulation efficiency were investigated. Under the optimal experimental conditions, the particle size was approximately 145 nm and encapsulation efficiency reached 92%. Moreover, the drug release of these nanoparticles could be prolonged over a significant period for more than ten days. It can be expected that this innovative approach could provide a useful platform for drug-loaded core–shell nanoparticles developing.
Survival of Streptococcus suis in Porcine Blood Is Limited by the Antibody- and Complement-Dependent Oxidative Burst Response of Granulocytes

Bacteremia is a hallmark of invasive Streptococcus suis infections of pigs, often leading to septicemia, meningitis, or arthritis. An important defense mechanism of neutrophils is the generation of reactive oxygen species (ROS). In this study, we report high levels of ROS production by blood granulocytes after intravenous infection of a pig with high levels of S. suis-specific antibodies and comparatively low levels of bacteremia. ABSTRACT Bacteremia is a hallmark of invasive Streptococcus suis infections of pigs, often leading to septicemia, meningitis, or arthritis. An important defense mechanism of neutrophils is the generation of reactive oxygen species (ROS). In this study, we report high levels of ROS production by blood granulocytes after intravenous infection of a pig with high levels of S. suis-specific antibodies and comparatively low levels of bacteremia. This prompted us to investigate the working hypothesis that the immunoglobulin-mediated oxidative burst contributes to the killing of S. suis in porcine blood. Several S. suis strains representing serotypes 2, 7, and 9 proved to be highly susceptible to the oxidative burst intermediate hydrogen peroxide, already at concentrations of 0.001%. The induction of ROS in granulocytes in ex vivo-infected reconstituted blood showed an association with pathogen-specific antibody levels. Importantly, inhibition of ROS production by the NADPH oxidase inhibitor apocynin led to significantly increased bacterial survival in the presence of high specific antibody levels. The oxidative burst rate of granulocytes partially depended on complement activation, as shown by specific inhibition. Furthermore, treatment of IgG-depleted serum with a specific IgM protease or heat to inactivate complement resulted in >3-fold decreased oxidative burst activity and increased bacterial survival in reconstituted porcine blood in accordance with an IgM-complement-oxidative burst axis. In conclusion, this study highlights an important control mechanism of S. suis bacteremia in the natural host: the induction of ROS in blood granulocytes via specific immunoglobulins such as IgM.
In vitro colonic fermentation of saponin-rich extracts from quinoa, lentil and fenugreek. Effect on sapogenins yield and human gut microbiota.

In vitro colonic fermentation of saponin-rich extracts from quinoa, lentil, and fenugreek was performed. Production of sapogenins by human fecal microbiota and the impact of extracts on representative intestinal bacterial groups were evaluated. The main sapogenins were found after fermentation (soyasapogenol B for lentil; oleanolic acid, hederagenin, phytolaccagenic acid and serjanic acid for quinoa; and sarsasapogenin, diosgenin and neotigogenin acetate for fenugreek). Interindividual differences were observed, but the highest production of sapogenins corresponded to quinoa (90 μg/mL) and fenugreek (70 μg/mL) extracts, being minor for lentil (4 μg/mL). Lentil and quinoa extracts showed a general antimicrobial effect, mainly on lactic acid bacteria and Lactobacillus spp. Significant increases of Bifidobacterium spp. and Lactobacillus spp. were observed for fenugreek in one volunteer. Thus, the transformation of saponin-rich extracts of quinoa, lentil and fenugreek to sapogenins by human gut microbiota is demonstrated, exhibiting a modulatory effect on the growth of selected intestinal bacteria.
Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease

Key Points Question Is the use of nilotinib hydrochloride, a drug approved for use in leukemia, safe and effective in patients with Parkinson disease? Findings In this randomized clinical trial of use of nilotinib hydrochloride in 75 patients with Parkinson disease, doses of 150 or 300 mg were reasonably safe and did not inhibit plasma Abelson tyrosine kinase. Twelve months of treatment with nilotinib altered exploratory cerebrospinal fluid biomarkers, including brain dopamine turnover, oligomeric α-synuclein, and hyperphosphorylated tau. Meaning This phase 2 trial met its objectives and nilotinib should be investigated in a phase 3 study as a potential disease-modifying therapy in Parkinson disease.
Should Thoracolumbar Junction be always Avoided as Upper Instrumented Vertebra in Long Instrumented Fusion for Adult Spinal Deformity?: Risk Factor Analysis for Proximal Junctional Failure.

: Age greater than 70 years, osteoporosis, and PJA greater 0° were identified as significant risk factors for PJF. Therefore, the TLJ level can be considered as UIV selectively for patients younger than 70 years without osteoporosis and with lordotic preoperative PJA. STUDY DESIGN Retrospective study OBJECTIVE. : To investigate the risk factors for proximal junctional failure (PJF) following long instrumented fusion stopping at thoracolumbar junction (TLJ) in adult spinal deformity (ASD) and to determine which cases are suitable for TLJ stop without increasing the risk for PJF. SUMMARY OF BACKGROUND DATA PJF following long fusion for ASD is a well-recognized complication that negatively affects clinical outcomes. Generally, the uppermost instrumented vertebra (UIV) at the TLJ is associated with the risk of PJF. Little is known about the risk factors for PJF in case with the UIV at TLJ. METHODS Radiographic and clinical data of 63 consecutive patients who underwent instrumented fusion from sacrum to TLJ (T11, T12, and L1) for the treatment of ASD with a minimum 2-year follow-up were analyzed to identify the risk factors for PJF, which was defined as proximal junctional angle (PJA) ≥ 20°, fracture at UIV or UIV+1, failure of UIV fixation, myelopathy, or need for proximal extension of fusion. RESULTS During the average follow-up duration of 51.7 months, PJF developed in 23 patients (36.5%) at a mean of 9.3 months after surgery. Multivariate analysis revealed that age greater than 70 years (OR, odds ratio: 1.119), osteoporosis (OR: 4.459), and preoperative kyphotic PJA (OR: 1.138) were significant risk factors for the development of PJF. No PJF occurred in 14 patients lacking any risk factors. The last follow-up clinical results were significantly inferior in the PJF group than in the non-PJF group in terms of ODI and SRS-22 score. CONCLUSIONS Age greater than 70 years, osteoporosis, and PJA greater 0° were identified as significant risk factors for PJF. Therefore, the TLJ level can be considered as UIV selectively for patients younger than 70 years without osteoporosis and with lordotic preoperative PJA. LEVEL OF EVIDENCE 3.
Alirocumab, evinacumab, and atorvastatin triple therapy regresses plaque lesions and improves lesion composition in mice[S]

Atherosclerosis-related CVD causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab, monoclonal antibodies against cholesterol-regulating proprotein convertase subtilisin/kexin type 9 and angiopoietin-like protein 3, may provide more benefit. We investigated the effect of such lipid-lowering interventions on atherosclerosis in APOE*3-Leiden.CETP mice, a well-established model for hyperlipidemia. Mice were fed a Western-type diet for 13 weeks and thereafter matched into a baseline group (euthanized at 13 weeks) and five groups that received diet alone (control) or with treatment [atorvastatin; atorvastatin and alirocumab; atorvastatin and evinacumab; or atorvastatin, alirocumab, and evinacumab (triple therapy)] for 25 weeks. We measured effects on cholesterol levels, plaque composition and morphology, monocyte adherence, and macrophage proliferation. All interventions reduced plasma total cholesterol (37% with atorvastatin to 80% with triple treatment; all P < 0.001). Triple treatment decreased non-HDL-C to 1.0 mmol/l (91% difference from control; P < 0.001). Atorvastatin reduced atherosclerosis progression by 28% versus control (P < 0.001); double treatment completely blocked progression and diminished lesion severity. Triple treatment regressed lesion size versus baseline in the thoracic aorta by 50% and the aortic root by 36% (both P < 0.05 vs. baseline), decreased macrophage accumulation through reduced proliferation, and abated lesion severity. Thus, high-intensive cholesterol-lowering triple treatment targeting all apoB-containing lipoproteins regresses atherosclerotic lesion area and improves lesion composition in mice, making it a promising potential approach for treating atherosclerosis.
Speckle tracking echocardiography in hypertensive males with glucose metabolism disorders

Aim. Early left ventricle (LV) abnormalities are hardly detectable by means of standard echocardiography in patients with hypertension (HTN) and glucose metabolism disorders. The objective of this study was to assess changes in LV function with speckle tracking echocardiography in hypertensive males with different types of glucose metabolism abnormalities. Methods and results. We recruited 158 hypertensive males with different glycemic status. The multidirectional LV strain was assessed by two-dimensional speckle tracking echocardiography. The patients with HTN and type 2 diabetes mellitus demonstrated signifi cant reduction of LV global longitudinal strain and early diastolic strain rate despite preserved LV ejection fraction. Conclusion. Speckle tracking echocardiography can identify subclinical myocardial alterations in hypertensive males with glucose metabolism abnormalities. Спекл-трекінг ехокардіографія в чоловіків з артеріальною гіпертензією та порушеннями метаболізму глюкози М. Ю. Колесник Стандартна ехокардіографія не має достатньої чутливості для оцінювання впливу порушень метаболізму глюкози на стан міокарда лівого шлуночка (ЛШ) у хворих з артеріальною гіпертензією. З метою оцінювання можливості ранньої діагностики субклінічного ураження міокарда ЛШ залучили до обстеження 158 чоловіків з артеріальною гіпертензією та різним глікемічним статусом, яким виконали спекл-трекінг ехокардіографію. Встановили, що у хворих на гіпертензію та цукровий діабет 2 типу реєструється вірогідне зменшення глобального поздовжнього стрейну та раннього діастолічного стрейн рейту ЛШ, незважаючи на збережену фракцію викиду ЛШ. Це свідчить про доцільність використання спекл-трекінг ехокардіографії у хворих з артеріальною гіпертензією та порушеннями метаболізму глюкози. Ключові слова: артеріальна гіпертензія, цукровий діабет 2 типу, порушення метаболізму глюкози, спекл-трекінг ехокардіографія. Запорізький медичний журнал. – 2014. – №6 (87). – С. 4–10
Immunosuppression in Cows following Intramammary Infusion of Mycoplasma bovis

Mycoplasma bovis is a destructive pathogen that causes large economic losses in rearing cattle for beef and dairy worldwide. M. bovis causes suppression of and evades the host immune response; however, the mechanisms of host immune function involved in M. bovis mastitis have not been elucidated. The purpose of this study was to elucidate the characteristics of the bovine immune response to mycoplasmal mastitis. We evaluated the responsiveness of the bovine mammary gland following infusion of M. bovis. ABSTRACT Mycoplasma bovis is a destructive pathogen that causes large economic losses in rearing cattle for beef and dairy worldwide. M. bovis causes suppression of and evades the host immune response; however, the mechanisms of host immune function involved in M. bovis mastitis have not been elucidated. The purpose of this study was to elucidate the characteristics of the bovine immune response to mycoplasmal mastitis. We evaluated the responsiveness of the bovine mammary gland following infusion of M. bovis. Somatic cell counts and bacterial counts in milk from the infected quarter were increased. However, the proliferation of peripheral blood mononuclear cells (blood MNCs) and mononuclear cells isolated from M. bovis-stimulated mammary lymph nodes (lymph node MNCs) did not differ from that in the unstimulated cells. Transcriptome analysis revealed that the mRNA levels of innate immune system-related genes in blood MNCs, complement factor D (CFD), ficolin 1 (FCN1), and tumor necrosis factor superfamily member 13 (TNFSF13) decreased following intramammary infusion of M. bovis. The mRNA levels of immune exhaustion-related genes, programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), lymphocyte activation gene 3 (LAG3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) of milk mononuclear cells (milk MNCs) in the infected quarter were increased compared with those before infusion. Increase in immune exhaustion-related gene expression and decrease in innate immune response-related genes of MNCs in quarters from cows were newly characterized by M. bovis-induced mastitis. These results suggested that M. bovis-induced mastitis affected the immune function of bovine MNCs, which is associated with prolonged duration of infection with M. bovis.
Differentiating Between Idiopathic Toe Walking and Cerebral Palsy: A Systematic Review

The purpose of this systematic review is to identify evidence-based examination components that enable a clinician to distinguish between children with idiopathic toe walking and cerebral palsy in order to accurately categorize them into their respective movement system diagnosis. Purpose: The purpose of this systematic review is to identify evidence-based examination components that enable a clinician to distinguish between participants with idiopathic toe walking (ITW) and cerebral palsy (CP) to accurately categorize them into their respective movement system diagnosis. Summary of Key Points: Five articles were used that compared key clinical findings, walking characteristics, and muscle firing patterns of participants with CP and ITW. Differences in these components allow participants with CP and ITW to be classified into different movement system diagnoses to better target plan of care. Conclusions and Recommendations for Clinical Practice: The authors recommend that clinicians perform specific evidence-based tests and measures in accordance with the International Classification of Functioning, Disability and Health model.
Corticosteroid use is not associated with improved outcomes in acute exacerbation of IPF

AE‐IPF has profound prognostic implications, preceding approximately half of all IPF‐related deaths. Despite this clinical significance, there are limited data to guide management decisions. Corticosteroids remain the mainstay of treatment despite a lack of strong supporting evidence and mounting concern that they may be harmful. We assessed the impact of corticosteroid therapy on in‐hospital mortality in AE‐IPF patients.
Immune mechanisms of fibrosis and inflammation in IgG4-related disease.

PURPOSE OF REVIEW To summarize recent advances in the understanding of the pathogenesis of IgG4-related disease. RECENT FINDINGS Limited data exist to explain genetic susceptibility to IgG4-related disease and the underlying triggers for this disease have not yet been identified. Cytotoxic CD4 T cells and activated B cells infiltrate affected organs and express proinflammatory and profibrotic molecules. Antigen presented by activated B cells likely reactivates cytotoxic CD4 T cells in disease tissues and these T cells in turn induce the targeted apoptotic death of host cells in certain organs - which presumably present the same antigenic peptide on Human Leukocyte Antigen class II molecules of relevance that was also presented on B cells during reactivation. A subsequent exaggerated tissue remodeling process is orchestrated by cytokines, chemokines, and enzymes secreted by both activated B cells and CD4CTLs. These molecules induce an overexuberant repair process resulting in fibrosis and loss of target organ function. SUMMARY In IgG4-related disease, presumably self-reactive cytotoxic CD4 T cells infiltrate tissues, are reactivated by T cells and induce apoptotic death. Molecules secreted by activated B cells and by CD4CTLs drive an exaggerated wound healing response resulting in fibrosis and compromised tissue function.
Methane and Carbon Dioxide Emission of Beef Heifers in Relation with Growth and Feed Efficiency

Simple Summary For sustainable meat production, beef farmers must make the best use of grass and roughage while limiting the carbon footprint of their herds. The genetic improvement in feed efficiency and enteric methane production of replacement heifers is possible if the recorded phenotypes are available. Intuitively, the relationship between the two traits should be negative, i.e., favorable, since the energy lost with the methane is not available for heifer metabolism. The measurement of feed efficiency requires several weeks of feed intake recording. The enteric methane emission rate can also be recorded over several weeks. The two traits of 326 beef heifers from two experimental farms were measured simultaneously for 8 to 12 weeks. The correlations between roughage intake, daily gain, and methane were all positive. The enteric methane emission rate was positively related to body weight, daily gain, and dry matter intake. The relationship with feed efficiency was slightly positive, i.e., unfavorable. Therefore, the two traits should be recorded simultaneously to evidence low-emitting and efficient heifers. This study also showed that replacing the feed intake recording with the carbon dioxide emission rate appeared potentially beneficial for selecting these low-emitting and efficient heifers. Abstract Reducing enteric methane production and improving the feed efficiency of heifers on roughage diets are important selection objectives for sustainable beef production. The objective of the current study was to assess the relationship between different methane production and feed efficiency criteria of beef heifers fed ad libitum roughage diets. A total of 326 Charolais heifers aged 22 months were controlled in two farms and fed either a grass silage (n = 252) or a natural meadow hay (n = 74) diet. Methane (CH4) and carbon dioxide (CO2) emission rates (g/day) were measured with GreenFeed systems. The dry matter intake (DMI), average daily gain (ADG), CH4 and CO2 were measured over 8 to 12 weeks. Positive correlations were observed among body weight, DMI, ADG, CH4 and CO2. The residual feed intake (rwgDMI) was not related to CH4 or residual methane (rwiCH4). It was negatively correlated with methane yield (CH4/DMI): Rp = −0.87 and −0.83. Residual gain (rwiADG) and ADG/DMI were weakly and positively related to residual methane (rwiCH4): Rp = 0.21 on average. The ratio ADG/CO2 appeared to be a useful proxy of ADG/DMI (Rp = 0.64 and 0.97) and CH4/CO2 a proxy of methane yield (Rp = 0.24 and 0.33) for selecting low-emitting and efficient heifers.
Rapid and quantitative detection of urinary Cyfra21-1 using fluorescent nanosphere-based immunochromatographic test strip for diagnosis and prognostic monitoring of bladder cancer

Abstract Bladder cancer is a common malignant tumour with high recurrence rate. Cytokeratin 19 fragments (Cyfra21-1) in urine has been regarded as a promising biomarker for the prognosis and diagnosis of bladder cancer due to the relevance of its high urinary level to the bladder cancer patients. However, currently detection methods of Cyfra21-1 have their limits, such as complicated steps, limited sensitivity or unsatisfying specificity. In this study, we developed a novel time-resolved fluoroimmuno test strip by using europium chelate microparticle (Eu-CM). Detection was performed in simple steps by carrying drops of sample into the well of the test strip, waiting for 15 min and inserting the strip into a fluorescence strip reader for quantitation. The standard curve equation of the test strip was y = 0.0177x + 0.01 (R 2 = .9993). In the analysis of human urine samples (n = 115), it demonstrated a good performance (accuracy: CV < 10%, AUC: 0.989). With the cut-off value of 81 ng/mL, the sensitivity and specificity for bladder cancer were 92.86 and 100%, respectively. In comparison to ELISA and electrochemiluminescence methods, the Eu-CM based time-resolved fluoroimmuno test strip provided a rapid, sensitive and reliable method for monitoring bladder cancer. It may be applied as a non-invasive approach for in point-of-care for bladder cancer detection.