Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron intake, serum iron indices and risk of colorectal adenomas: a meta‐analysis of observational studies

&NA; To provide a quantitative assessment of the association between iron intake, serum iron indices and the risk of colorectal adenoma (CRA), we summarised the evidence from observational studies. Relevant studies were identified in MEDLINE and EMBASE until 31 March 2015. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random‐effects model. A total of 10 articles, involving 3318 subjects with CRA, were used in this meta‐analysis. The SRR of CRA was 0.83 (95% CI: 0.71‐0.98; Pheterogeneity = 0.694, I2 = 0) for the highest versus the lowest level of dietary iron intake. The SRR was 0.93 (95% CI: 0.62‐1.42) for total (dietary and supplemental) iron intake, 1.23 (95% CI: 1.03‐1.48) for haem iron intake and 0.73 (95% CI: 0.54‐0.97) for supplemental iron intake. Serum iron indices were not associated with CRA risk (serum ferritin: SRR = 1.16, 95% CI: 0.81‐1.66; serum iron: SRR = 1.02, 95% CI: 0.75‐1.38; serum transferrin saturation: SRR = 1.01; 95% CI: 0.82‐1.50). Increased intake of haem iron is associated with significantly increased risk of CRA, whereas intake of non‐haem or supplemental iron is inversely associated with risk of CRA. Limited data indicate null associations between serum iron indices and CRA risk.
Quality is the key for emerging issues of population-based colonoscopy screening

Colonoscopy is currently regarded as the gold standard and preferred method of screening for colorectal cancer (CRC). However, the benefit of colonoscopy screening may be blunted by low participation rates in population-based screening programs. Harmful effects of population-based colonoscopy screening may include complications induced by colonoscopy itself and by sedation, psychosocial distress, potential over-diagnosis, and socioeconomic burden. In addition, harmful effects of colonoscopy may increase with age and comorbidities. As the risk of adverse events in population-based colonoscopy screening may offset the benefit, the adverse events should be managed and monitored. To adopt population-based colonoscopy screening, consensus on the risks and benefits should be developed, focusing on potential harm, patient preference, socioeconomic considerations, and quality improvement of colonoscopy, as well as efficacy for CRC prevention. As suboptimal colonoscopy quality is a major pitfall of population-based screening, adequate training and regulation of screening colonoscopists should be the first step in minimizing variations in quality. Gastroenterologists should promote quality improvement, auditing, and training for colonoscopy in a population-based screening program.
Lack of Clinical Utility of Urine Gram Stain for Suspected Urinary Tract Infection in Pediatric Patients

ABSTRACT Urinary tract infection (UTI) is one of the most common infections in children. Urine culture remains the gold standard for diagnosis, but the utility of urine Gram stain relative to urinalysis (UA) is unclear. We reviewed 312 pediatric patients with suspected UTI who had urine culture, UA, and urine Gram stain performed from a single urine specimen. UA was considered positive if ≥10 leukocytes per oil immersion field were seen or if either nitrates or leukocyte esterase testing was positive. Urine Gram stain was considered positive if any organisms were seen. Sensitivity, specificity, and positive and negative predictive values were calculated using urine culture as the gold standard. Thirty-seven (12%) patients had a culture-proven UTI. Compared to urine Gram stain, UA had equal sensitivity (97.3% versus 97.5%) and higher specificity (85% versus 74%). Empirical therapy was prescribed before the Gram stain result was known in 40 (49%) patients and after in 42 (51%) patients. The antibiotics chosen did not differ between the two groups (P = 0.81), nor did they differ for patients with Gram-negative rods on urine Gram stain compared to those with Gram-positive cocci (P = 0.67). From these data, we conclude that UA has excellent negative predictive value that is not enhanced by urine Gram stain and that antibiotic selection did not vary based on the urine Gram stain result. In conclusion, the clinical utility of urine Gram stain does not warrant the time or cost it requires.
Applications of high‐resolution magic angle spinning MRS in biomedical studies I—cell line and animal models

High‐resolution magic angle spinning (HRMAS) MRS allows for direct measurements of non‐liquid tissue and cell specimens to present valuable insights into the cellular metabolisms of physiological and pathological processes. HRMAS produces high‐resolution spectra comparable to those obtained from solutions of specimen extracts but without complex metabolite extraction processes, and preserves the tissue cellular structure in a form suitable for pathological examinations following spectroscopic analysis. The technique has been applied in a wide variety of biomedical and biochemical studies and become one of the major platforms of metabolomic studies. By quantifying single metabolites, metabolite ratios, or metabolic profiles in their entirety, HRMAS presents promising possibilities for diagnosis and prediction of clinical outcomes for various diseases, as well as deciphering of metabolic changes resulting from drug therapies or xenobiotic interactions. In this review, we evaluate HRMAS MRS results on animal models and cell lines reported in the literature, and present the diverse applications of the method for the understanding of pathological processes and the effectiveness of therapies, development of disease animal models, and new progress in HRMAS methodology.
Chemosensory function before and after multimodal treatment in chronic rhinosinusitis patients

Olfactory dysfunction is common among the general population, with chronic rhinosinusitis (CRS) as one of the leading causes. Patients affected by CRS often report changes in taste sensations; however, quantitative measurements have not been performed to date. Therefore, the present study aimed to investigate gustatory and olfactory function in CRS patients prior to and after multimodal treatment.
CLINICAL FEATURES COMORBIDITY OF ALCOHOL AND SUBSTANCE DEPENDENCE WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD)

Aims:Attention-deficit/hyperactivity disorder (ADHD) is of great clinical importance not only because of its high preva- lence but also due to the frequent comorbid illnesses that are connected with this disorder. Several studies were able to demonstrate that ADHD constitutes a significant risk factor for the exacerbation of habit-forming illnesses, i.e. addictions. Methods: We conducted a study on 152 adult patients with alcohol dependence (n = 91) or multiple substance addiction (n = 61) to determine whether or not these patients were affected by ADHD. For retrospective assessment of childhood ADHD, the WURS-k was used as well as the DSM-IV symptom checklist for ADHD. The CAARS was used to assess the persisting symptoms of ADHD in adults. Results: 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the alcohol-dependent patients showed evidence of retrospective ADHD affliction in child- hood. With the help of CAARS, ADHD was proved to be persistent in 33.3% of the adult patients. In the group of substance-addicted patients50.8%(WURS-k)and54.1%(DSM-IV)presentedwithdiagnosticcriteriaforADHDinchildhoodand65.5%(CAARS)showed evidence of ADHD persisting in adulthood. Conclusions: These results reveal that habit-forming illnesses can be associated with a high comorbidity with ADHD, expressed in the form of alcohol abuse and also in consumption of illegal drugs. The results underline the great importance of early and adequate diagnostics and therapy of ADHD for the prevention of habit-forming illnesses.
A Fuzzy Restricted Boltzmann Machine: Novel Learning Algorithms Based on the Crisp Possibilistic Mean Value of Fuzzy Numbers

A fuzzy restricted Boltzmann machine (FRBM) is extended from a restricted Boltzmann machine (RBM) by replacing all the real-valued parameters with fuzzy numbers. A new FRBM that employs the crisp possibilistic mean value of a fuzzy number to defuzzify the fuzzy free energy function is presented. This approach is much clearer and easier to obtain the expression of the defuzzified free energy function and its approximation than the centroid method. Several theorems that discuss the error bounds of the approximation to ensure the rationality and validity are also investigated. Learning algorithms are given for the designed FRBM with symmetric triangular fuzzy numbers (STFNs), asymmetric triangular fuzzy numbers, and Gaussian fuzzy numbers. By appropriately choosing the parameters, a theorem is concluded that all FRBMs with symmetric fuzzy numbers will have identical learning algorithm to that of FRBMs with STFNs. This is illustrated by a case of FRBM with Gaussian fuzzy numbers. Two experiments including the MNIST handwriting recognition and the Bars-and-Stripes benchmark are carried out. The results show that the proposed FRBMs significantly outperform RBMs in learning accuracy and generalization ability, especially when encountering unlearned samples and recovering incomplete images.
BET Proteins: An Approach to Future Therapies in Transplantation

In order to develop new efficient therapies for organ transplantation, it is essential to acquire a comprehensive knowledge of the molecular mechanisms and processes, such as immune activation, chronic inflammation, and fibrosis, which lead to rejection and long‐term graft loss. Recent efforts have shed some light on the epigenetic regulation associated with these processes. In this context, the bromo and extraterminal (BET) family of bromodomain proteins (BRD2, BRD3, BRD4, and BRDT) have emerged as major epigenetic players, connecting chromatin structure with gene expression changes. These proteins recognize acetylated lysines in histones and master transcription factors to recruit regulatory complex and, finally, modify the transcriptional program. Recent studies indicate that BET proteins are essential in the NF‐kB‐mediated inflammatory response, during the activation and differentiation of Th17‐immune cells, and in profibrotic processes. Here, we review this new body of data and highlight the efficiency of BET inhibitors in several models of diseases. The promising results obtained from these preclinical models indicate that it may be time to translate these outcomes to the transplantation field, where epigenetics will be of increasing value in the coming years.
Sensitivity Characterization of a COTS 90-nm SRAM at Ultralow Bias Voltage

This paper presents the characterization of the sensitivity to 14-MeV neutrons of a commercial off-the-shelf 90-nm static random access memories manufactured by Cypress Semiconductor, when biased at ultralow voltage. First, experiments exposing this memory at 14-MeV neutrons, when powering it up at bias voltages ranging from 0.5 to 3.3 V, are presented and discussed. These results are in good concordance with theoretical predictions issued by the modeling tool <italic>MUlti-SCAles Single Event Phenomena Predictive Platform</italic>. Then, this tool has been used to obtain soft error rate predictions at different altitudes above the Earth’s surface of this device versus its bias voltage. Finally, the effect of contamination by <inline-formula> <tex-math notation="LaTeX">$\alpha $ </tex-math></inline-formula> particles has also been estimated at said range of bias voltages.
A Bayesian decision theoretic model of sequential experimentation with delayed response

We propose a Bayesian decision theoretic model of a fully sequential experiment in which the real‐valued primary end point is observed with delay. The goal is to identify the sequential experiment which maximizes the expected benefits of technology adoption decisions, minus sampling costs. The solution yields a unified policy defining the optimal ‘do not experiment’–‘fixed sample size experiment’–‘sequential experiment’ regions and optimal stopping boundaries for sequential sampling, as a function of the prior mean benefit and the size of the delay. We apply the model to the field of medical statistics, using data from published clinical trials.
Micromechanical Modeling of Granular Soil at Small Strain by Arrays of Elastic Spheres.

Abstract : The need for a micromechanical approach to modeling the stress-strain response of granular soil is discussed and justified. This work focuses on the small shear strain behavior, and investigates the validity of modeling analytically uniform, rounded-grained quartz and by arrays of identical elastic, rough, quartz spheres. As a first step, the stress-strain properties of six regular arrays of spheres are studied in some detail, with focus on isotropic and biaxial boundary loading. Keywords: Particular mechanics; Regular arrays of spheres; Self consistent method; Stress-strain relationships; Isotropy, Transverse isotropy; Small strains; Threshold strain/P-waves; Shear modulus.
Capturing Breathy Voice: Durational Measures of Oral Stops in Marathi

The present study investigates a series of techniques used to capture the durational differences of oral stops in Marathi, an Indic language that exhibits a four-way phonemic distinction among oral stops. Like many of its Indic relatives, Marathi utilizes both voicing and aspiration to achieve oral stop contrasts, yielding aspirated and plain versions of both voiced and voiceless stops. While voice onset time (VOT) is an acoustic feature which can be reliably used to distinguish between plain voiced, plain voiceless, and aspirated voiceless stops, it does not help to differentiate between plain voiced and aspirated voiced—or breathy-voiced—stops. While durational differences may not be sufficient in and of themselves, they do contribute acoustic cues that aid in establishing the four-way contrast. With this in mind, the present production study investigates the utility of two alternative acoustic measures of duration that have been proposed: Noise Offset Time (NOT), proposed by Davis (1994), is measured from the release burst to the beginning of the second formant in the following vowel. The After Closure Time (ACT), proposed by Mikuteit and Reetz (2007), is measured from the release burst to the beginning of periodicity in the waveform. Six native speakers of Marathi were recorded producing a randomized word-list that contained Marathi oral stops in word-initial position before [a]. The digitized recordings were fed into PRAAT, and waveforms and spectrograms were used to measure the ACT and the NOT of each stop. While there is some utility to each measurement, this study suggests that neither is completely clear cut; speaker variation means that the hallmarks of the waveform or spectrogram consulted to take each measurement are sometimes absent or open to subjectivity. A new measurement that takes advantage of the consistently present elements of both the ACT and the NOT is proposed. This measure, referred to as the Pre-vocalic Interval (PVI), is measured from the release burst to the jump in intensity which coincides with the appearance of clear formants in the spectrogram of the following vowel.
NDFIP allows NEDD4/NEDD4L-induced AQP2 ubiquitination and degradation

Regulation of our water homeostasis is fine-tuned by dynamic translocation of Aquaporin-2 (AQP2)-bearing vesicles to and from the plasma membrane of renal principal cells. Whereas binding of vasopressin to its type-2 receptor initiates a cAMP-protein kinase A cascade and AQP2 translocation to the apical membrane, this is counteracted by protein kinase C-activating hormones, resulting in ubiquitination-dependent internalization of AQP2. The proteins targeting AQP2 for ubiquitin-mediated degradation are unknown. In collecting duct mpkCCD cells, siRNA knockdown of NEDD4 and NEDD4L E3 ligases yielded increased AQP2 abundance, but they did not bind AQP2. Membrane Yeast Two-Hybrid assays using full-length AQP2 as bait, identified NEDD4 family interacting protein 2 (NDFIP2) to bind AQP2. NDFIP2 and its homologue NDFIP1 have PY motifs by which they bind NEDD4 family members and bring them close to target proteins. In HEK293 cells, NDFIP1 and NDFIP2 bound AQP2 and were essential for NEDD4/NEDD4L-mediated ubiquitination and degradation of AQP2, an effect not observed with PY-lacking NDFIP1/2 proteins. In mpkCCD cells, downregulation of NDFIP1, NEDD4 and NEDD4L, but not NDFIP2, increased AQP2 abundance. In mouse kidney, Ndfip1 and Ndfip2 mRNA distribution was similar and high in proximal tubules and collecting ducts, which was also found for NDFIP1 proteins. Our results reveal that NEDD4/NEDD4L mediate ubiquitination and degradation of AQP2, but that NDFIP proteins are needed to connect NEDD4/NEDD4L to AQP2. As NDFIP1/2 bind many NEDD4 family E3 ligases, which are implicated in several cellular processes, NDFIP1/2 may be the missing link for AQP2 ubiquitination and degradation from different subcellular locations.
Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy

Preclinical models suggest that histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors have synergistic anticancer activity. We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of combined mTOR inhibitor sirolimus (1 mg-5 mg PO daily) and HDAC inhibitor vorinostat (100 mg-400 mg PO daily) in patients with advanced cancer. Seventy patients were enrolled and 46 (66%) were evaluable for DLT assessment since they completed cycle 1 without dose modification unless they had DLT. DLTs comprised grade 4 thrombocytopenia (n = 6) and grade 3 mucositis (n = 1). Sirolimus 4 mg and vorinostat 300 mg was declared RP2D because MTD with sirolimus 5 mg caused significant thrombocytopenia. The grade 3 and 4 drug-related toxic effects (including DLTs) were thrombocytopenia (31%), neutropenia (8%), anemia (7%), fatigue (3%), mucositis (1%), diarrhea (1%), and hyperglycemia (1%). Of the 70 patients, 35 (50%) required dose interruption or modification and 61 were evaluable for response. Partial responses were observed in refractory Hodgkin lymphoma (−78%) and perivascular epithelioid tumor (−54%), and stable disease in hepatocellular carcinoma and fibromyxoid sarcoma. In conclusion, the combination of sirolimus and vorinostat was feasible, with thrombocytopenia as the main DLT. Preliminary anticancer activity was observed in patients with refractory Hodgkin lymphoma, perivascular epithelioid tumor, and hepatocellular carcinoma.
Effect of morphine on the RNA and ATP concentration of brain structures of the rat.

The effect of morphine on rat cortical, hippocampal, thalamic, and hypothalamic RNA and ATP concentration was studied. After a single dose (10 mg/kg, i.p.) there was an increase of RNA in the cortex and thalamus, and a decrease of ATP levels in both structures. When the drug was given chronically (daily injections during 10 days at increasing doses from 10 to 100 mg/kg), only a fall of thalamic RNA and an increase of thalamic ATP were observed relative to saline-treated controls. Rats which received the chronic saline treatment, however, had higher hippocampal thalamic RNA and levels and a lower thalamic ATP concentration than those which received a single saline Injection.
lukSF-PV in Staphylococcus aureus keratitis isolates and association with clinical outcome.

PURPOSE To determine the prevalence, genetic diversity, and clinical relevance of the lukSF-PV gene, encoding the bacterial toxin Panton-Valentine leukocidin, in Staphylococcus aureus isolates from cases of bacterial keratitis in the United Kingdom. METHODS Multiplex PCRs investigating carriage of lukSF-PV and mecA were performed on S. aureus isolates from patients. The lukSF-PV operon was sequenced to investigate its diversity, and multilocus sequence typing to test for a clonal relationship between lukSF-PV isolates. Antimicrobial minimum inhibitory concentrations (MICs) and clinical outcome data were compared for isolates characterized as lukSF-PV+ve, mecA+ve, and lukSF-PV/mecA-ve. RESULTS Of 95 isolates, 9 (9.5%) were lukSF-PV+ve, 9 (9.5%) mecA+ve, and 1 was positive for both. Five single nucleotide polymorphisms were found in lukSF-PV genes of seven strains. There was no significant difference between the MICs of lukSF-PV/mecA-ve and lukSF-PV+ve isolates to the antimicrobials tested, except for tigecycline (P < 0.05). The mecA+ve isolates had significantly higher mean MICs to meropenem and fluoroquinolones (P < 0.05). There were nonsignificant trends for healing and treatment times, ulcer and scar size, and overall clinical score to be greater in the lukSF-PV+ve group (P < 0.05). The proportion of patients, however, who required surgery was significantly greater among patients with lukSF-PV+ve isolates with an odds ratio of 7.8 (95% CI 1-42, P = 0.018) for patients requiring surgery. CONCLUSIONS lukSF-PV+ve isolates were associated with a trend to worse clinical outcome and more surgical interventions, with an effect unrelated to MICs. This suggests that lukSF-PV may be an important virulence factor in S. aureus-associated keratitis.
Transfusion-associated adverse reactions (TAARs) and cytokine accumulations in the stored blood components: the impact of prestorage versus poststorage leukoreduction

Leukoreduction in blood units could prevent patients undergoing transfusions from transfusion-associated adverse reactions (TAARs) such as febrile nonhemolytic transfusion reactions (FNHTRs). However, the effect of prestorage and poststorage leukoreduction on TAARs and its underlying mechanisms in stored blood components remains to be determined. Therefore, we investigated the impact of prestorage leukocyte-reduced (pre-LR) and poststorage leukocyte-reduced (post-LR) blood products, including red blood cells (RBCs) and apheresis platelets (PHs), on the incidence of FNHTRs and other TAARs in patients who received transfusions from 2009 to 2014 in a tertiary care center. We also investigated the difference of leukocyte-related bioactive mediators between pre- and post-LR blood components. The results indicated that prevalence of TAARs was significantly reduced in the transfusions of pre-LR blood components. Particularly, the prevalence of FNHTRs was significantly reduced in the pre-LR RBC transfusions and the prevalence of allergy reactions was markedly reduced in the pre-LR PH transfusions. Furthermore, in vitro evaluation of cytokines in the pre- and post-LR blood components revealed that IL-1β, IL-8 and RANTES levels were significantly elevated in the post-LR RBCs during the storage. In contrast, IL-1β, IL-6 and IL-8 levels were significantly elevated in the post-LR PHs during the storage. These findings suggested that prestorage leukoreduction had a diminishing effect on the development of TAARs, which could be associated with less accumulation of cytokines in the stored blood components.
Prospective Observational Study of Incidence and Preventable Burden of Childhood Tuberculosis, Kenya

Prospective data on childhood tuberculosis (TB) incidence and case detection rates (CDRs) are scant, and the pre ventable burden of childhood TB has not been measured in prospective studies. We investigated 2,042 children (<15 years of age) with suspected TB by using enhanced sur veillance and linked hospital, demographic, notification, and verbal autopsy data to estimate the incidence, CDR, risk factors, and preventable burden of TB among children in Kenya. Estimated TB incidence was 53 cases/100,000 children/year locally and 95 cases/100,000 children/year nationally. The estimated CDR was 0.20–0.35. Among chil dren <5 years of age, 49% of cases were attributable to a known household contact with TB. This study provides much needed empiric data on TB CDRs in children to inform national and global incidence estimates. Moreover, our find ings indicate that nearly half of TB cases in young children might be prevented by implementing existing guidelines for TB contact tracing and chemoprophylaxis. of