Miracle-dz/UniFAR-FTUs huggingface dataset:
The predictive value of the product of contrast medium volume and urinary albumin/creatinine ratio in contrast-induced acute kidney injury

Abstract Preexisting renal impairment and the amount of contrast media are the most important risk factors for contrast-induced acute kidney injury (CI-AKI). We aimed to investigate whether the product of contrast medium volume and urinary albumin/creatinine ratio (CMV × UACR) would be a better predictor of CI-AKI in patients undergoing nonemergency coronary interventions. This was a prospective single-center observational study, and 912 consecutive patients who were exposed to contrast media during coronary interventions were investigated prospectively. CI-AKI is defined as a 44.2 μmol/L rise in serum creatinine or a 25% increase, assessed within 48 h after administration of contrast media in the absence of other causes. Fifty patients (5.48%) developed CI-AKI. The urinary albumin/creatinine ratio (UACR) (OR = 1.002, 95% CI = 1.000–1.003, p = .012) and contrast medium volume (CMV) (OR = 1.008, 95% CI = 1.001–1.014, p = .017) were independent risk factors for the development of CI-AKI. The area under the ROC curve of CMV, UACR and CMV × UACR were 0.662 (95% CI = 0.584–0.741, p < .001), 0.761 (95% CI = 0.674–0.847, p < .001) and 0.808 (95% CI = 0.747–0.896, p < .001), respectively. The cutoff value of CMV × UACR to predict CI-AKI was 1186.2, with 80.0% sensitivity and 62.2% specificity. The product of CMV and UACR (CMV × UACR) might be a predictor of CI-AKI in patients undergoing nonemergency coronary interventions, which was superior to CMV or UACR alone.
Structure of the Varicella Zoster Virus Thymidylate Synthase Establishes Functional and Structural Similarities as the Human Enzyme and Potentiates Itself as a Target of Brivudine

Varicella zoster virus (VZV) is a highly infectious human herpesvirus that is the causative agent for chicken pox and shingles. VZV encodes a functional thymidylate synthase (TS), which is the sole enzyme that produces dTMP from dUMP de novo. To study substrate binding, the complex structure of TSVZV with dUMP was determined to a resolution of 2.9 Å. In the absence of a folate co-substrate, dUMP binds in the conserved TS active site and is coordinated similarly as in the human encoded TS (TSHS) in an open conformation. The interactions between TSVZV with dUMP and a cofactor analog, raltitrexed, were also studied using differential scanning fluorimetry (DSF), suggesting that TSVZV binds dUMP and raltitrexed in a sequential binding mode like other TS. The DSF also revealed interactions between TSVZV and in vitro phosphorylated brivudine (BVDUP), a highly potent anti-herpesvirus drug against VZV infections. The binding of BVDUP to TSVZV was further confirmed by the complex structure of TSVZV and BVDUP solved at a resolution of 2.9 Å. BVDUP binds similarly as dUMP in the TSHS but it induces a closed conformation of the active site. The structure supports that the 5-bromovinyl substituent on BVDUP is likely to inhibit TSVZV by preventing the transfer of a methylene group from its cofactor and the subsequent formation of dTMP. The interactions between TSVZV and BVDUP are consistent with that TSVZV is indeed a target of brivudine in vivo. The work also provided the structural basis for rational design of more specific TSVZV inhibitors.
Predicting Hospitalization and Outpatient Corticosteroid Use in Inflammatory Bowel Disease Patients Using Machine Learning.

Background Inflammatory bowel disease (IBD) is a chronic disease characterized by unpredictable episodes of flares and periods of remission. Tools that accurately predict disease course would substantially aid therapeutic decision-making. This study aims to construct a model that accurately predicts the combined end point of outpatient corticosteroid use and hospitalizations as a surrogate for IBD flare. Methods Predictors evaluated included age, sex, race, use of corticosteroid-sparing immunosuppressive medications (immunomodulators and/or anti-TNF), longitudinal laboratory data, and number of previous IBD-related hospitalizations and outpatient corticosteroid prescriptions. We constructed models using logistic regression and machine learning methods (random forest [RF]) to predict the combined end point of hospitalization and/or corticosteroid use for IBD within 6 months. Results We identified 20,368 Veterans Health Administration patients with the first (index) IBD diagnosis between 2002 and 2009. Area under the receiver operating characteristic curve (AuROC) for the baseline logistic regression model was 0.68 (95% confidence interval [CI], 0.67-0.68). AuROC for the RF longitudinal model was 0.85 (95% CI, 0.84-0.85). AuROC for the RF longitudinal model using previous hospitalization or steroid use was 0.87 (95% CI, 0.87-0.88). The 5 leading independent risk factors for future hospitalization or steroid use were age, mean serum albumin, immunosuppressive medication use, and mean and highest platelet counts. Previous hospitalization and corticosteroid use were highly predictive when included in specified models. Conclusions A novel machine learning model substantially improved our ability to predict IBD-related hospitalization and outpatient steroid use. This model could be used at point of care to distinguish patients at high and low risk for disease flare, allowing individualized therapeutic management.
A novel antibody targeting sequence 31–35 in amyloid β protein attenuates Alzheimer's disease‐related neuronal damage

Amyloid β protein (Aβ) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31–35 in Aβ molecule is an effective active center responsible for Aβ neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31–35 of amyloid β protein, and investigated the neuroprotection of the anti‐Aβ31–35 antibody against Aβ1–42‐induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats. The results showed that the anti‐Aβ31–35 antibody almost equally bound to both Aβ31–35 and Aβ1–42, and pretreatment with the antibody dose‐dependently prevented Aβ1–42‐induced cytotoxicity on cultured primary cortical neurons. In behavioral study, intracerebroventricular (i.c.v.) injection of anti‐Aβ31–35 antibody efficiently attenuated Aβ1–42‐induced impairments in spatial learning and memory of rats. In vivo electrophysiological experiments further indicated that Aβ1–42‐induced suppression of hippocampal synaptic plasticity was effectively reversed by the antibody. These results demonstrated that the sequence 31–35 of Aβ may be a new therapeutic target, and the anti‐Aβ31–35 antibody could be a novel immunotheraputic approach for the treatment of AD. © 2016 Wiley Periodicals, Inc.
Accurate disulfide-bonding network predictions improve ab initio structure prediction of cysteine-rich proteins

MOTIVATION Cysteine-rich proteins cover many important families in nature but there are currently no methods specifically designed for modeling the structure of these proteins. The accuracy of disulfide connectivity pattern prediction, particularly for the proteins of higher-order connections, e.g., >3 bonds, is too low to effectively assist structure assembly simulations. RESULTS We propose a new hierarchical order reduction protocol called Cyscon for disulfide-bonding prediction. The most confident disulfide bonds are first identified and bonding prediction is then focused on the remaining cysteine residues based on SVR training. Compared with purely machine learning-based approaches, Cyscon improved the average accuracy of connectivity pattern prediction by 21.9%. For proteins with more than 5 disulfide bonds, Cyscon improved the accuracy by 585% on the benchmark set of PDBCYS. When applied to 158 non-redundant cysteine-rich proteins, Cyscon predictions helped increase (or decrease) the TM-score (or RMSD) of the ab initio QUARK modeling by 12.1% (or 14.4%). This result demonstrates a new avenue to improve the ab initio structure modeling for cysteine-rich proteins. AVAILABILITY AND IMPLEMENTATION http://www.csbio. sjtu.edu. cn/bioinf/Cyscon/ CONTACT zhng@umich.edu or hbshen@sjtu.edu. cn. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
History and Clinical Validation of the PASCAL ® Dynamic Contour Tonometer

Will Goldmann Applanation Tonometry, the age old “gold standard” of intraocular pressure (IOP) measurement, be replaced with newer methods? One of the newer methods of IOP measurement is Pascal, dynamic contour tonometry (DCT). A review of the history, scientific principles, clinical validation and clinical utility of DCT is presented.
Correlation of High-Resolution CT, Symptoms, and Pulmonary Function in Patients During Recovery From Severe Acute Respiratory Syndrome

Study objectives: Little is known of the nature of the recovery period after severe acute respiratory syndrome (SARS) infection. We hypothesized that structural changes of the lung might correlate with symptoms and pulmonary function. To answer this question, we correlate findings of high-resolution CT (HRCT) with dyspnea scores and results of pulmonary function tests in patients during recovery from SARS. Design: Retrospective follow-up cohort study. Setting: University hospital. Patients: Nineteen patients who recovered from SARS-related hospitalization. Measurements: The study included HRCT scores (0 to 100), dyspnea scores (1 to 4), static and dynamic lung volumes, and diffusing capacity of the lung for carbon monoxide (Dlco). Results: The interval between hospital discharge and HRCT study or functional assessment was 31.2 ± 4.8 days (range, 25 to 38 days) [mean ± SD]. All patients had HRCT abnormalities and were assigned to two groups: ground-glass opacity (GGO) only (n = 7, 36.8%) and GGO with fibrosis (GGO+F) [n = 12, 63.2%]. Most patients (16 of 19, 84.2%) had no zonal predominance. HRCT scores correlated well with dyspnea scores (r = 0.78, p < 0.01) and with a variety of pulmonary functional variables, with Dlco being the most significant (r = − 0.923, p < 0.001). Compared with the GGO group, the GGO+F group showed significantly lower FEV1, FVC, total lung capacity, residual volume, and Dlco. Conclusions: HRCT findings correlate well with functional studies and clinical symptoms during recovery from SARS. Longer-term follow-up studies in a larger cohort of patients should be performed to investigate the clinical outcome of recovered SARS patients.
Prevention of Acute Kidney Injury in Children Undergoing Cardiac Surgery: A Narrative Review

Children undergoing cardiac surgery are at risk of developing acute kidney injury (AKI). Preventing cardiac surgery–associated AKI (CS-AKI) is important as it is associated with increased early- and long-term mortality and morbidity. Targeting modifiable risk factors (eg, avoiding poor renal perfusion, nephrotoxic drugs, and fluid overload) reduces the risk of CS-AKI. There is currently no strong evidence for the routine use of pharmacological approaches (eg, aminophylline, dexmedetomidine, fenoldopam, and steroids) to prevent CS-AKI. There is robust evidence to support the role of early peritoneal dialysis as a nonpharmacologic approach to prevent CS-AKI.
Fatigue behavior of A5052 aluminum alloy with diamond-like carbon/electroless nickel plating hybrid coating

Electroless nickel plating was formed on A5052 aluminum alloy, and subsequently diamond-like carbon (DLC) was deposited on nickel plating to fabricate DLC/nickel plating hybrid coating. Cantilever rotating bending fatigue tests were conducted using the specimens with and without coatings. The fatigue strengths of the specimens with DLC or nickel plating single layers were higher than those of the substrate without coating. However, the specimens with nickel plating had large scatter in the fatigue strengths due to some cracking in the coatings. When DLC was deposited on the nickel-plating layer, the fatigue strengths were further improved compared with the specimens with DLC or nickel plating single layers. The observation of fatigue fracture surfaces revealed that fatigue crack initiated at the substrate just beneath the coating in the specimens with DLC or nickel plating single layers. However, subsurface fatigue crack initiation occurred in high cycle fatigue regime of the specimen with hybrid coating. It indicated that the improvement of fatigue strengths could be attributed to the suppression of fatigue crack initiation by coatings, where hybrid coating was more efficient than DLC or nickel plating single layers.
Isorhamnetin and Quercetin Derivatives as Anti-Acetylcholinesterase Principles of Marigold (Calendula officinalis) Flowers and Preparations

Marigold (Calendula officinalis L.) is one of the most common and widespread plants used medicinally all over the world. The present study aimed to evaluate the anti-acetylcholinesterase activity of marigold flowers, detect the compounds responsible and perform chemical analysis of marigold commercial products. Analysis of 23 varieties of C. officinalis flowers introduced into Siberia allowed us to select the Greenheart Orange variety due to the superior content of flavonoids (46.87 mg/g) and the highest inhibitory activity against acetylcholinesterase (IC50 63.52 µg/mL). Flavonoids, isorhamnetin and quercetin derivatives were revealed as potential inhibitors with the application of high-performance liquid chromatography (HPLC) activity-based profiling. Investigation of the inhibitory activity of isorhamnetin glycosides demonstrated the maximal potency for isorhamnetin-3-O-(2′′,6′′-di-acetyl)-glucoside (IC50 51.26 μM) and minimal potency for typhaneoside (isorhamnetin-3-O-(2′′,6′′-di-rhamnosyl)-glucoside; IC50 94.92 µM). Among quercetin derivatives, the most active compound was quercetin-3-O-(2′′,6′′-di-acetyl)-glucoside (IC50 36.47 µM), and the least active component was manghaslin (quercetin-3-O-(2′′,6′′-di-rhamnosyl)-glucoside; IC50 94.92 µM). Some structure-activity relationships were discussed. Analysis of commercial marigold formulations revealed a reduced flavonoid content (from 7.18–19.85 mg/g) compared with introduced varieties. Liquid extract was the most enriched preparation, characterized by 3.10 mg/mL of total flavonoid content, and infusion was the least enriched formulation (0.41 mg/mL). The presented results suggest that isorhamnetin and quercetin and its glycosides can be considered as potential anti-acetylcholinesterase agents.
Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction: Evidence Meets Practice, Part II

Pharmacologic treatment for systolic heart failure, otherwise known as heart failure with reduced ejection fraction, has been established through clinical trials and is formulated into guidelines to standardize the diagnosis and treatment. Since the introduction of angiotensin-converting enzyme inhibitors and vasodilators in the 1980s, many guideline-recommended therapies have emerged over the past 20 years targeting specific neurohormones, aldosterone, and catecholamines to treat heart failure. Part 2 of this series will describe &bgr;-blockers, digoxin, and aldosterone antagonists in the context of the mechanism of action in heart failure, investigational trials that showed beneficial effects, and the practical applications for clinical use.
Adipose‐derived stem cells decrease cardiomyocyte damage induced by porphyromonas gingivalis endotoxin through suppressing hypertrophy, apoptosis, fibrosis, and MAPK markers

Heart failure is one of the complications related to periodontal disease. In addition to drugs or herbal medicines, stem cell therapy shows potential in the treatment of cardiomyopathy. This study investigates if stem cells exhibit beneficial effects on cardiomyocyte damage induced by porphyromonas gingivalis endotoxin (Pg‐LPS). From the experimental results we find that Pg‐LPS reduce cardiomyocyte viability via the activation of apoptosis, hypertrophy, fibrosis and MAPK signaling. Pg‐LPS damaged cardiomyocytes co‐cultured with adipose‐derived stem cells (ADSC) increases cardiomyocyte viability through suppressing the pathological markers described above. Further evidence implies that survival marker, IGF1, secreted from ADSC, may play an important role in the Pg‐LPS induced protective effect on cardiomyocyte damage.
EffectiveSan: type and memory error detection using dynamically typed C/C++

Low-level programming languages with weak/static type systems, such as C and C++, are vulnerable to errors relating to the misuse of memory at runtime, such as (sub-)object bounds overflows, (re)use-after-free, and type confusion. Such errors account for many security and other undefined behavior bugs for programs written in these languages. In this paper, we introduce the notion of dynamically typed C/C++, which aims to detect such errors by dynamically checking the "effective type" of each object before use at runtime. We also present an implementation of dynamically typed C/C++ in the form of the Effective Type Sanitizer (EffectiveSan). EffectiveSan enforces type and memory safety using a combination of low-fat pointers, type meta data and type/bounds check instrumentation. We evaluate EffectiveSan against the SPEC2006 benchmark suite and the Firefox web browser, and detect several new type and memory errors. We also show that EffectiveSan achieves high compatibility and reasonable overheads for the given error coverage. Finally, we highlight that EffectiveSan is one of only a few tools that can detect sub-object bounds errors, and uses a novel approach (dynamic type checking) to do so.
Liquid Compared With Conventional Cervical Cytology: A Systematic Review and Meta-analysis

OBJECTIVE: To compare test performance characteristics of conventional Pap tests and liquid-based cervical cytology samples. DATA SOURCES: Eligible studies, published between 1991 and 2007, were retrieved through PubMed/EmBase searching and completed by consultation of other sources. METHODS OF STUDY SELECTION: Studies were selected if a conventional and a liquid-based sample were prepared from the same woman or when one or the other type of sample was taken from a separate but similar cohort. The current systematic review and meta-analysis is restricted to studies where all subjects were submitted to gold standard verification, based on colposcopy and histology of colposcopy-targeted biopsies, allowing computation of absolute and relative test validity for cervical intraepithelial neoplasia grade 2 or worse. Randomized trials were selected as well if all test-positive cases were verified with the same gold standard, allowing computation of the relative sensitivity. Impact of study characteristics on accuracy was assessed by subgroup meta-analyses, meta-regression, and summary receiver operating characteristic curve regression. TABULATION, INTEGRATION, AND RESULTS: The relative sensitivity, pooled from eight studies, with complete gold standard verification and from one randomized clinical trial, did not differ significantly from unity. Also, the specificity, considering high-grade and low-grade squamous intraepithelial lesions as cutoff, was similar in conventional and liquid cytology. However, a lower pooled specificity was found for liquid-based cytology when presence of atypical squamous cells of undetermined significance was the cutoff (ratio 0.91, 95% confidence interval 0.84–0.98). Differences in study characteristics did not explain interstudy heterogeneity. CONCLUSION: Liquid-based cervical cytology is neither more sensitive nor more specific for detection of high-grade cervical intraepithelial neoplasia compared with the conventional Pap test.
Structural and Maturational Covariance in Early Childhood Brain Development

Abstract Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co‐activation in functional networks may guide and refine the maturation of SCNs over childhood development.
Antimicrobial Agents Used in the Treatment of Peri-Implantitis Alter the Physicochemistry and Cytocompatibility of Titanium Surfaces.

BACKGROUND Chemotherapeutic agents (ChAs) are considered an integral part of current treatment protocols for the decontamination of titanium implants with peri-implantitis, based on their antimicrobial effect. Despite the proven antimicrobial effect of ChAs on titanium-bound biofilms, previous studies have elucidated an unexpected disassociation between bacterial reduction and biologically acceptable treatment outcomes. In this study, the authors hypothesize that ChAs residues alter titanium physicochemistry and thus compromise cellular response to decontaminated surfaces. METHODS Grit-blasted acid-etched titanium disks were contaminated with multispecies microcosm biofilms grown from in vivo peri-implant plaque samples. To simulate implant decontamination, the contaminated disks were burnished with 0.12% chlorhexidine, 20% citric acid, 24% EDTA/1.5% NaOCl, or sterile saline and assessed surface physicochemical properties. Sterile untreated surfaces were the controls. The biologic effects of decontamination were assessed via cell proliferation and differentiation assays. RESULTS Bacterial counts after decontamination confirmed that the ChAs were antimicrobial. X-ray photoelectron spectroscopy invariably detected elemental contaminants associated with each ChA molecule or salt that significantly altered wettability compared with controls. Notably, all surfaces with ChA residues showed some cytotoxic effect compared with controls (P <0.05). Increased cell counts were consistently found in the saline-treated group compared with chlorhexidine (P = 0.03). Interestingly, no association was found between antimicrobial effect and cell counts (P >0.05). CONCLUSIONS ChA-specific residues left on the titanium surfaces altered titanium physical properties and adversely affected the osteoblastic response irrespective of their observed antimicrobial effect. Chlorhexidine may compromise the biocompatibility of titanium surfaces, and its use is not recommended to detoxify implants. Sterile saline, citric acid, and NaOCl-EDTA may be proposed for use in the treatment of peri-implantitis. Contrary to previous studies that recommended the selection of ChAs for the decontamination of titanium implants according to their antimicrobial effects, the present study demonstrated that the restoration of the biocompatibility of contaminated titanium surfaces is also contingent on the preservation of titanium material properties.