Miracle-dz/UniFAR-FTUs huggingface dataset:
The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade

Abstract Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.
The Farnesoid X Receptor Agonist Tropifexor Prevents Liver Damage in Parenteral Nutrition-fed Neonatal Piglets

Supplemental Digital Content is available in the text ABSTRACT Objectives: Intestinal failure-associated liver disease (IFALD) is a life-threatening complication for patients with intestinal failure who receive long-term parenteral nutrition (PN). We evaluated the effects of the farnesoid X receptor agonist tropifexor on a neonatal piglet model of IFALD fed with PN. Methods: The piglets received PN and tropifexor for 14 days, then levels of liver enzymes, bile acid metabolism, inflammation, and intestinal barrier markers were assessed using quantitative real-time PCR. Fibroblast growth factor (FGF) 19 serum levels were determined using enzyme-linked immunosorbent assays. Bile acids were determined in liver, serum, and intestinal contents, and the microbiome was sequenced in different intestinal segments. Results: The PN model was established in newborn piglets. The levels of serum liver enzymes, pro-inflammatory factors, and oxidative stress increased in the livers of piglets fed with PN, but not in those fed with PN and tropifexor. Tropifexor stimulated FGF19 expression in ileal epithelial cells, increased portal FGF19 levels, then inhibited cholesterol 7α-hydroxylase expression in the liver. Tropifexor increased the relative abundance of bacteria associated with bile salt hydrolase and 7α-dehydrogenation in the contents of ileum and altered the composition of bile acids in serum, liver, and intestinal contents. Tropifexor also inhibited intestinal inflammation, alleviated intestinal mucosal atrophy, and improved the intestinal barrier. Conclusions: Tropifexor might prevent liver damage in neonatal piglets receiving PN by altering the composition of intestinal microbiota and bile acids. Tropifexor also alleviates intestinal inflammation and preserves the intestinal barrier.
Management of Pediatric Acute Dacryocystitis

Purpose: To analyze the clinical presentation, course, and management in a large cohort of pediatric acute dacryocystitis subjects and to examine whether hospitalization and urgent surgical intervention are indeed mandatory. Methods: A retrospective analysis of all pediatric subjects diagnosed with dacryocystitis at the Children’s Hospital of Philadelphia over a 12-year period (2009–2020). Results: One-hundred sixty-nine pediatric acute dacryocystitis patients were included in this study. Management included admission in 117 cases (69%). Sixty-eight patients (40%) were treated medically with no surgical intervention, 75 cases (44%) required urgent surgical intervention, and 26 additional cases (15%) required surgery due to persistent tearing symptoms after medical management. The urgent procedures included most commonly: 1) endonasal examination and microdebridement of intranasal cysts in 26 cases (35%); 2) probing and irrigation without examination and microdebridement, with or without stent intubation, in 30 cases (40%); and 3) dacryocystorhinostomy (13 endonasal and 4 external) in 17 cases (23%). Conclusions: Management of pediatric acute dacryocystitis should be tailored individually for each case. Hospital admission and early surgical intervention are not mandatory, as 31% of cases resolved without admission, and 56% without early surgical intervention. Although a specific age cutoff is not plausible, hospital admission for younger patients is more commonly advocated. When surgical intervention is indicated, endonasal examination and microdebridement of any associated intranasal cyst and probing with possible stenting are the initial procedures of choice. Dacryocystorhinostomy is reserved for more complex obstructions. Although pediatric acute dacryocystitis is an infection with serious potential problems, when managed appropriately, complications are rare. Acute pediatric dacryocystitis can initially be managed with medical treatment alone, particularly for patients older than 1 year of age; when surgical intervention is indicated, endonasal examination is helpful to diagnose and treat associated intranasal cysts.
Spatiotemporal patterns of gene expression around implanted silicon electrode arrays

Objective. Intracortical brain interfaces are an ever evolving technology with growing potential for clinical and research applications. The chronic tissue response to these devices traditionally has been characterized by glial scarring, inflammation, oxidative stress, neuronal loss, and blood-brain barrier disruptions. The full complexity of the tissue response to implanted devices is still under investigation. Approach. In this study, we have utilized RNA-sequencing to identify the spatiotemporal gene expression patterns in interfacial (within 100 µm) and distal (500 µm from implant) brain tissue around implanted silicon microelectrode arrays. Naïve, unimplanted tissue served as a control. Main results. The data revealed significant overall differential expression (DE) in contrasts comparing interfacial tissue vs naïve (157 DE genes), interfacial vs distal (94 DE genes), and distal vs naïve tissues (21 DE genes). Our results captured previously characterized mechanisms of the foreign body response, such as astroglial encapsulation, as well as novel mechanisms which have not yet been characterized in the context of indwelling neurotechnologies. In particular, we have observed perturbations in multiple neuron-associated genes which potentially impact the intrinsic function and structure of neurons at the device interface. In addition to neuron-associated genes, the results presented in this study identified significant DE in genes which are associated with oligodendrocyte, microglia, and astrocyte involvement in the chronic tissue response. Significance. The results of this study increase the fundamental understanding of the complexity of tissue response in the brain and provide an expanded toolkit for future investigation into the bio-integration of implanted electronics with tissues in the central nervous system.
Monitoring Water Quality Using Benthic Macroinvertebrates and Physicochemical Parameters of Behzat Stream in Turkey

The present work reports the results of an intensive study on water quality and bentic macroinverte brate fauna of Behzat Stream in Turkey. The research was carried out at five sampling sites of two different sections of the stream between September 1998 and September 2002. A total of 52 macroinvertebrate taxa were recorded. The upper section supported a more diverse community than the lower section. A low macroinvertebrate abundance was observed during summer in the lower section, this would be the result of high values of phosphate and nitrogen ions. in spite of this, Behzat Stream showed good water quality condi tions. At the present it is under threat of anthropogenic disturbances, this especially in the lower section.
Impact of a physician – critical care practitioner pre‐hospital service in Wales on trauma survival: a retrospective analysis of linked registry data

The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre‐hospital doctors and advanced critical care practitioners to the scene of time‐critical life‐ and limb‐threatening incidents to provide advanced decision‐making and pre‐hospital clinical care. The impact of the service on 30‐day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate‐to‐severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre‐hospital management by the Emergency Medical Retrieval and Transfer Service and 30‐day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30‐day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre‐hospital care services. However, after adjustment for differences in case‐mix, the 30‐day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41–0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30‐day mortality for patients with blunt traumatic injury.
Effect of Memantine Treatment and Combination with Vitamin D Supplementation on Body Composition in the APP/PS1 Mouse Model of Alzheimer's Disease Following Chronic Vitamin D Deficiency.

BACKGROUND Vitamin D deficiency and altered body composition are common in Alzheimer's disease (AD). Memantine with vitamin D supplementation can protect cortical axons against amyloid-β exposure and glutamate toxicity. OBJECTIVE To study the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on whole-body composition using a mouse model of AD. METHODS Male APPswe/PS1dE9 mice were divided into four groups at 2.5 months of age: the control group (n = 14) was fed a standard diet throughout; the remaining mice were started on a vitamin D-deficient diet at month 6. The vitamin D-deficient group (n = 14) remained on the vitamin D-deficient diet for the rest of the study. Of the remaining two groups, one had memantine (n = 14), while the other had both memantine and 10 IU/g vitamin D (n = 14), added to their diet at month 9. Serum 25(OH)D levels measured at months 6, 9, 12, and 15 confirmed vitamin D levels were lower in mice on vitamin D-deficient diets and higher in the vitamin D-supplemented mice. Micro-computed tomography was performed at month 15 to determine whole-body composition. RESULTS In mice deprived of vitamin D, memantine increased bone mineral content (8.7% increase, p < 0.01) and absolute skeletal tissue mass (9.3% increase, p < 0.05) and volume (9.2% increase, p < 0.05) relative to controls. This was not observed when memantine treatment was combined with vitamin D enrichment. CONCLUSION Combination treatment of vitamin D and memantine had no negative effects on body composition. Future studies should clarify whether vitamin D status impacts the effects of memantine treatment on bone physiology in people with AD.
Coffee consumption and colorectal cancer risk: a multicentre case-control study from Italy and Spain

Background: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent. Aim: To provide further information on the risk of colorectal cancer in relation to coffee consumption. Methods: Data derive from two companion case-control studies conducted in Italy and Spain within the European Union Project on Health Impacts of long-term exposure to disinfection by-products in Drinking Water and the Spanish Multi-Case Control study on Cancer. These included a total of 2289 incident cases with colorectal cancer and 3995 controls with information on coffee intake. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from unconditional logistic regression models, adjusted for study centre, sex, age, education, smoking, and other covariates. Results: Compared with never coffee drinkers, the OR was 0.99 (95% CI 0.95–1.02) for total coffee consumption. There was no significant trend in risk with dose or duration, the ORs being 0.95 (95% CI 0.72–1.25) for an amount of five or more cups per day of coffee and 0.95 (95% CI 0.75–1.19) for a duration of consumption of 50 years or longer. The OR was 1.04 (95% CI 0.87–1.25) for two or more cups per day of decaffeinated coffee. There were no heterogeneity across strata of various covariates, as well as no apparent differences between various anatomical subsites. Conclusion: This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk.
Minimally Invasive Versus Sternotomy for Mitral Surgery in the Elderly: A Systematic Review and Meta-Analysis

Objective The safety of minimally invasive mitral valve surgery (MIMVS) in elderly patients is still debated. Our objective was to perform a systematic review and meta-analysis of studies comparing MIMVS with conventional sternotomy (CS) in elderly patients (≥65 years old). Methods We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and Cochrane Central Register of Controlled Trials for trials and observational studies comparing MIMVS with CS in patients ≥65 years old presenting for mitral valve surgery. We performed a random-effects meta-analysis of all outcomes. Results The MIMVS group had lower odds of acute renal failure (odds ratio [OR] 0.27; 95% CI 0.10 to 0.78), prolonged intubation (>48 h; OR 0.47; 95% CI 0.31 to 0.70), less blood product transfusion (weighted mean difference [WMD] −0.82 units; 95% CI −1.29 to −0.34 units), shorter ICU length of stay (LOS; WMD −2.57 days; 95% CI −3.24 to −1.90 days) and hospital LOS (WMD −4.06 days; 95% CI −5.19 to −2.94 days). There were no significant differences in the odds of mortality, stroke, respiratory infection, reoperation for bleeding, and postoperative atrial fibrillation. MIMVS was associated with longer cross-clamp (WMD 11.8 min; 95% CI 3.5 to 20.1 min) and cardiopulmonary bypass times (WMD 23.0 min; 95% CI 10.4 to 35.6 min). Conclusions MIMVS in elderly patients is associated with lower postoperative complications, blood transfusion, shorter ICU, and hospital LOS, and longer cross-clamp and bypass times.
Adherence to Guideline-Concordant Care and Its Effect on Survival in Black patients with Head and Neck Cancers: A SEER-Medicare Analysis.

BACKGROUND In head and neck squamous cell carcinoma (HNSCC), black patients continue to have worse survival when compared to white patients. The cause of this disparity is multifaceted and cannot be explained by one etiology alone. To investigate this disparity, we utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine adherence to guideline concordant care (GCC) as defined by the National Comprehensive Cancer Network (NCCN). PATIENTS AND METHODS In this retrospective study, Medicare beneficiaries diagnosed with non-metastatic HNSCC as their first cancer between 1992 and 2011, and a random sample of Medicare controls matched to cases (2:1) diagnosed between 2004 and 2011 (N=16378), were included in this analysis. RESULTS Black patients were less likely to receive GCC in advanced stage oropharyngeal (66%vs.74%;p=0.007) and oral cavity (56%vs.71%;p=0.002) SCC. On multivariate analysis, black patients demonstrated an increased risk of death in advanced oropharyngeal (p<0.001), oral cavity (p=0.01), and hypopharyngeal (p=0.01) SCC. CONCLUSION Black patients did not consistently receive GCC across HNSCC subsites, contributing to the poorer outcomes seen when compared to white patients. Future research should focus on elucidating the mechanisms behind the non-GCC given to black HNSCC patients and other factors that may contribute to this disparity such as tumor biology. IMPLICATIONS FOR PRACTICE Black patients with head and neck cancer (HNC) continue to have worse survival than white patients. We examined if the racial disparity in survival from curable HNC is affected by adherence to guideline-concordant care (GCC). We discovered that black patients were less likely to receive appropriate treatment in certain HNCs. Although adherence to proper therapy was associated with improved survival in HNC patients, the difference in survival, where black patients had inferior outcomes, remained. This analysis uncovered a major contributor to the disparity seen in HNC patients. As such, cancer centers serving a predominantly black HNC population, can design specific clinical interventions to ensure GCC for all patients, potentially improving outcomes for everyone.
X‐ray photoelectron spectroscopy and time‐of‐flight secondary ion mass spectrometry characterization of aging effects on the mineral fibers treated with aminopropylsilane and quaternary ammonium compounds

X‐ray photoelectron spectroscopy (XPS) and time‐of‐flight secondary ion mass spectrometry were used to investigate the aging effects on the aminopropylsilane (APS) and quaternary ammonium surfactant‐treated mineral fibers. APS‐coated mineral fiber samples were treated with cationic surfactant and mineral oil and aged at 70 °C temperature and 95% humidity. From quantitative XPS measurements, an increase in the atomic composition of oxygen, nitrogen, and silicon is observed after aging. An increase in the protonated amino groups in the N1s high‐resolution spectra and C–N group in the C1s high‐resolution spectra is also observed. These results indicate that the concentration of hydrocarbon groups decreases after aging due to the partial removal of the long hydrocarbon chains of the surfactant and mineral oil and/or hydrolysis and segregation of APS to the fiber surface. The principal component analysis (PCA) was applied to the time‐of‐flight secondary ion mass spectrometry spectra, and an increase in the intensities of APS characteristic peaks were observed after aging. The observed increase in the signals of APS originates from underlying silanized fibers after the removal of the surfactant and mineral oil from the surface. Copyright © 2012 John Wiley & Sons, Ltd.
Feasibility and Therapeutic Potential of Combined Peptide Receptor Radionuclide Therapy With Intensive Chemotherapy for Pediatric Patients With Relapsed or Refractory Metastatic Neuroblastoma

Background Recent evidence has demonstrated high expression of somatostatin receptors in neuroblastoma (NB) cells. Because of this, we endeavored to evaluate the diagnostic performance and clinical efficacy of 68Ga-DOTATATE PET/CT and peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE combined with chemotherapy in pediatric NB patients. Patients and Methods In total, 14 pediatric patients with histopathologically confirmed NB underwent 68Ga-DOTATATE PET/CT. Among them, the patients who were refractory or relapsed after therapy with 131I-MIBG and had intensive uptake of 68Ga-DOTATATE were referred for PRRT using 177Lu-DOTATATE. Treatment response based on follow-up imaging was classified into complete response, partial response, stable disease, and progressive disease. After each cycle of PRRT, laboratory tests were performed for evaluation of hematological, renal, and hepatic toxicities. The CTCAE (Common Terminology Criteria for Adverse Events; version 4.03) was used for grading adverse event. Curie score and International Society of Pediatric Oncology Europe Neuroblastoma score were used for semiquantitative analysis of scans of patients who underwent PRRT. In addition, overall survival was calculated as the time interval between the date of the first cycle and the end of follow-up or death. Results Overall, 14 refractory NB children including 7 boys and 7 girls with a median age of 5.5 years (ranged from 4 to 9) underwent 68Ga-DOTATATE PET/CT. PET/CT was positive in 10/14 patients (71.4%), and the median number of detected lesions in positive patients was 2 (range, 1–13). Of 14 patients, 5 patients underwent PRRT, including 3 boys and 2 girls. A total of 19 PRRT cycles and 66.4 GBq 177Lu-DOTATATE were given. Among these 5 patients, 2 showed an initial complete response, which relapsed a few months later, 1 showed a partial response, and 2 showed progressive disease. According to the Kaplan-Meier test, the overall survival was estimated at 14.5 months (95% confidence interval, 8.9–20.1). In evaluation of PRRT-related toxicity according to the CTCAE, 4 patients showed grade 1, and 1 showed grade 2 leukopenia. Two patients showed grade 1, and 2 others showed grade 2 anemia. Two patients showed grade 1, and 3 patients showed grade 2 thrombocytopenia. Serum creatinine in 1 patient increased to grade 1. Conclusions Combination of 177Lu-DOTATATE with chemotherapeutic agents might achieve worthwhile responses with low toxicity, encouraging survival in NB patients who have relapsed or are refractory to conventional therapy, including 131I-MIBG therapy. Imaging with 68Ga-DOTATATE PET/CT in such patients has a relatively high detection efficacy, demonstrating its potential use as an alternative imaging tool to conventional modalities such as 123I/131I-MIBG. However, further well-designed trials are highly warranted.
Role of job and personal resources in the appraisal of job demands as challenges and hindrances

Previous research has shown that challenge and hindrance job demands show different effects on employees’ wellbeing and performance. Moreover, it has been demonstrated that employees’ subjective appraisal of job demands as challenges and hindrances may vary: they can be appraised as challenges or hindrances or both. Subjective appraisal of job demands was found to be also related to employees’ wellbeing and productivity. However, little is known about predictors of the appraisals of job demands made by employees. The aim of the study was to identify predictors of such appraisals among job and individual resources. Cross-sectional research was carried out among 426 IT, healthcare and public transport employees. COPSOQ II scales were used to measure job demands (emotional, quantitative, cognitive demands, work pace and role conflicts) and job resources (influence at work, possibilities for development, vertical and horizontal trust), single questions were used to measure employees’ subjective appraisals of job demands as hindrances and challenges, and PCQ was used to measure psychological capital. Multiple hierarchical regression analyses showed that only horizontal trust predicted the appraisal of job demands as challenges, and vertical trust predicted the appraisal of job demands as hindrances among four analysed job resources. Individual resource–psychological capital–predicted only the appraisal of job demands as challenges. Control variables–occupation, age and job demands also played a significant role in predicting the appraisal of job demands. Implications and future directions are discussed.