Miracle-dz/UniFAR-FTUs huggingface dataset:
Esophageal intraepithelial invasion of Helicobacter pylori correlates with atypical hyperplasia

Helicobacter pylori (H. pylori), a common pathogen residing in the gastrointestinal tract, has been well characterized in stomach cancer,while its correlation with esophageal cancer remains poorly understood. In this study, we aim to assess the relationship between esophageal intraepithelial H. pylori invasion and inflammation as well as atypical hyperplasia in esophageal squamous epithelial tissues. Esophageal squamous cell carcinoma (ESCC) tissue samples from 196 individuals from both southern and northern esophageal carcinoma high‐risk areas in China were examined (125 from northern high‐risk areas, 71 from southern high‐risk area), while additional 30 samples were collected adjacent to the esophageal squamous cell carcinoma (A‐ESCC). H. pylori infection was identified by Giemsa staining, immuno‐histochemical staining, and H. pylori 16S rRNA‐based PCR. A significant increase of H. pylori infection was found in tumor tissues (including ESCC and A‐ESCC samples) compared to that of non‐tumor tissues (p < 0.05). The positive rate of H. pylori 16S rRNA in ESCC, A‐ESCC, and normal groups were 62.5, 74.1, and 26.7%, respectively. The PCR results showed that the positive incidence of the H. pylori virulence factor CagA gene in tumor (ESCC and A‐ESCC) and normal groups was 54.9 and 20%, respectively (p < 0.05). To explore the possible causes of CagA+ H. pylori infection leading to carcinogenesis, we found that CagA+ H. pylori filtrate induced DNA strand breaks in esophageal epithelial NE3 cells, suggesting that H. pylori infection may be an original cause leading to atypical hyperplasia of esophageal squamous epithelial tissues and contributed to pathological carcinogenesis of ESCC.
C-B3-02: Primary and Early Non-Adherence in an HMO Population

Background Adherence to prescribed medications is associated with improved health outcomes in many chronic conditions. Measures of adherence typically depend on administrative data from pharmacy dispensing databases and require a minimum of two drug dispensings to calculate (ongoing adherence). Patients who do not pick up the initial prescription (primary non-adherers) or who fill it only once (early non-adherers) are excluded from calculations based on pharmacy databases. Reasons for non-adherence in primary and early non-adherent patients could be different from those in patients with ongoing dispensings who discontinue or who are not fully adherent to their medications and could vary across diseases or drug classes. Aim To characterize primary and early non-adherers among a population of patients with diabetes, hypertension, and/or hyperlipidemia enrolled in an integrated health system. Methods We identified Kaiser Permanente Colorado (KPCO) members with a newly-initiated order for a medication of interest in 2007 and 2008. Orders were identified using electronic health record data; these orders were sent to the pharmacy information management system (PIMS). From PIMS we determined if/ when dispensing occurred. We classified patients into ongoing adherence and primary and early non-adherence groups. If patients had new orders for more than one drug of interest, we classified them as early or primary non-adherers only if they were not in the ongoing adherence group for any of the drugs. Patients were also classified according to drug group (antidiabetic, antihypertensive, antihyperlipidemic, or multi-drug). Results Of 15,417 patients with a newly-initiated order for a drug of interest, 1147 (7.4%) were in the primary non-adherence group and 3355 (21.8%) were early non-adherers. Individuals initiated on more than one drug were most likely to be in the ongoing dispensing group. Almost 10% (754 of 7636) of individuals prescribed an anti-diabetic or antihyperlipidemic drug did not fill their first prescription, twice as many as among those prescribed an antihypertensive drug. Conclusions Excluding the relatively large proportion of patients who do not receive ongoing dispensings of a newly-initiated drug yields an incomplete picture of medication adherence and thereby the potential factors contributing to non-adherence. For example, we found primary non-adherence differed across therapeutic classes.
Dietary intake of artificial sweeteners by the Belgian population

This study investigated whether the Belgian population older than 15 years is at risk of exceeding ADI levels for acesulfame-K, saccharin, cyclamate, aspartame and sucralose through an assessment of usual dietary intake of artificial sweeteners and specific consumption of table-top sweeteners. A conservative Tier 2 approach, for which an extensive label survey was performed, showed that mean usual intake was significantly lower than the respective ADIs for all sweeteners. Even consumers with high intakes were not exposed to excessive levels, as relative intakes at the 95th percentile (p95) were 31% for acesulfame-K, 13% for aspartame, 30% for cyclamate, 17% for saccharin, and 16% for sucralose of the respective ADIs. Assessment of intake using a Tier 3 approach was preceded by optimisation and validation of an analytical method based on liquid chromatography with mass spectrometric detection. Concentrations of sweeteners in various food matrices and table-top sweeteners were determined and mean positive concentration values were included in the Tier 3 approach, leading to relative intakes at p95 of 17% for acesulfame-K, 5% for aspartame, 25% for cyclamate, 11% for saccharin, and 7% for sucralose of the corresponding ADIs. The contribution of table-top sweeteners to the total usual intake (<1% of ADI) was negligible. A comparison of observed intake for the total population with intake for diabetics (acesulfame-K: 3.55 versus 3.75; aspartame: 6.77 versus 6.53; cyclamate: 1.97 versus 2.06; saccharine: 1.14 versus 0.97; sucralose: 3.08 versus 3.03, expressed as mg kg−1 bodyweight day−1 at p95) showed that the latter group was not exposed to higher levels. It was concluded that the Belgian population is not at risk of exceeding the established ADIs for sweeteners.
Effect of recombinant human insulin-like growth factor-I on progression of ALS

The objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the treatment of sporadic ALS. A double-blind, placebo-controlled, randomized study of 266 patients was conducted at eight centers in North America. Placebo or rhIGF-I(0.05 mg/kg/day or 0.10 mg/kg/day) was administered for 9 months. The primary outcome measure was disease symptom progression, assessed by the rate of change (per patient slope) in the Appel ALS rating scale total score. The Sickness Impact Profile (SIP), a patient-perceived, health-related quality of life assessment, was a secondary outcome variable. Progression of functional impairment in patients receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than in patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined markers of disease symptom progression, and members in this group exhibited a slower decline in quality of life, as assessed by the SIP. Patients receiving 0.05 mg/kg/day of rhIGF-I exhibited trends similar to those associated with high-dose treatment, suggesting a dose-dependent response. The incidence of clinically significant adverse experiences was comparable among the three treatment groups. Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects.
Characterisation of aflatoxin and deoxynivalenol exposure among pregnant Egyptian women

Mycotoxins such as the aflatoxins and deoxynivalenol (DON) are frequent contaminants of food. Aflatoxin B1 (AFB1) and DON affect the immune system and restrict growth; additionally AFB1 is carcinogenic. To date there are limited descriptive biomarker data concerning maternal exposures during pregnancy, and none on co-exposures to these mycotoxins. This survey was a cross-sectional assessment providing descriptive data on the concentrations of serum aflatoxin–albumin (AF-alb), urinary aflatoxin M1 (AFM1), and urinary DON for 98 pregnant women from Egypt, in relation to diet and socioeconomic status, during the third trimester. AF-alb was detected in 34 of 98 (35%) samples, geometric mean (GM) of positives = 4.9 pg AF-lys mg−1 albumin (95% confidence interval (CI) = 4.1–5.8 pg mg−1), and AFM1 in 44 of 93 (48%) samples, GM of positives = 19.7 pg mg−1 creatinine (95%CI = 14.8–26.3 pg mg−1). AF-alb and AFM1 levels were positively correlated (R = 0.276, p = 0.007). DON was detected in 63 of 93 (68%), GM of positives = 2.8 ng mg−1 (95%CI = 2.1–3.6 ng mg−1). Aflatoxin and DON biomarkers were observed in 41% of the subjects concurrently. The frequency and level of these biomarkers in Egyptian women were modest compared with known high-risk countries. However, this study represents the first biomarker survey to report on the occurrence of DON biomarkers in an African population, in addition to the co-occurrence of these two potent mycotoxins. This combined exposure may be of particular concern during pregnancy given the potential of toxin transfer to the foetus.
Analysis of fumonisin contamination and the presence of Fusarium in wheat with kernel black point disease in the United States

The ability of the fungus Fusarium proliferatum to cause kernel black point disease in wheat was previously established, but natural contamination of black point wheat with both F. proliferatum and fumonisin mycotoxins has not been studied in the United States. Low levels of fumonisins were detected in nine of 43 wheat samples with kernel black point disease that were obtained from across the United States. A subset of samples was contaminated with F. proliferatum as well as with F. fujikuroi, F. nygamai, F. thapsinum and F. verticillioides, species closely related to F. proliferatum and morphologically similar to it in that they produce chains of asexual spores, or conidia. Nevertheless, of conidial chain-forming fusaria isolated from symptomatic wheat, F. proliferatum dominated. In greenhouse tests, isolates of F. proliferatum and the other species recovered from wheat samples were able to cause symptoms of kernel black point and, in some cases, low levels of fumonisin contamination of wheat. These data add to the understanding of the risk of fumonisin contamination of wheat and the potential for Fusarium species to cause kernel black point disease and fumonisin contamination of wheat. Further, the results of this study indicate that while US-grown wheat can sporadically be contaminated by fumonisins, the natural contamination levels seem to be low. The observations made provide evidence that fumonisins are not likely to be a factor contributing to the ability of Fusarium to cause kernel black point disease.
Targeting glutamine transport to suppress melanoma cell growth

Amino acids, especially leucine and glutamine, are important for tumor cell growth, survival and metabolism. A range of different transporters deliver each specific amino acid into cells, some of which are increased in cancer. These amino acids consequently activate the mTORC1 pathway and drive cell cycle progression. The leucine transporter LAT1/4F2hc heterodimer assembles as part of a large complex with the glutamine transporter ASCT2 to transport amino acids. In this study, we show that the expression of LAT1 and ASCT2 is significantly increased in human melanoma samples and is present in both BRAFWT (C8161 and WM852) and BRAFV600E mutant (1205Lu and 451Lu) melanoma cell lines. While inhibition of LAT1 by BCH did not suppress melanoma cell growth, the ASCT2 inhibitor BenSer significantly reduced both leucine and glutamine transport in melanoma cells, leading to inhibition of mTORC1 signaling. Cell proliferation and cell cycle progression were significantly reduced in the presence of BenSer in melanoma cells in 2D and 3D cell culture. This included reduced expression of the cell cycle regulators CDK1 and UBE2C. The importance of ASCT2 expression in melanoma was confirmed by shRNA knockdown, which inhibited glutamine uptake, mTORC1 signaling and cell proliferation. Taken together, our study demonstrates that ASCT2‐mediated glutamine transport is a potential therapeutic target for both BRAFWT and BRAFV600E melanoma.
The Effect of Chronic Ultraviolet Radiation on the Human Immune System †

A single or a limited number of UVR exposures is recognized to suppress cell‐mediated immunity in human subjects. The complex pathway leading from the absorption of photons by chromophores in the skin to the generation of T regulatory cells has been, at least partially, elucidated. However, the effect of repeated UV exposures on immune responses and associated mediators is not well studied, particularly to assess whether they lead, first, to the development of photoprotection so that these immune changes are reduced or no longer occur, and, secondly, to the development of photoprotection against the normal downregulation of immunity induced by a high UV dose. For almost all the parameters evaluated in this review—epidermal DNA damage/erythema, urocanic acid, Langerhans and dendritic cells, natural killer cells, macrophages, mast cells, contact and delayed hypersensitivity responses—none, aside from epidermal DNA damage/erythema and macrophage phagocytic activity, show convincing evidence of photoadaptation or, where appropriate, photoprotection. It is concluded that repeatedly irradiating individuals with UVR is likely to continue to result in downregulation of immunity.
High‐grade cervical abnormalities and cervical cancer in women following a negative Pap smear with and without an endocervical component: A cohort study with 10 years of follow‐up

The proportion of Pap smears containing an endocervical component (ECC) has been declining in Australia. Given that ECC negative (ECC−) smears may be associated with reduced sensitivity, we undertook a retrospective cohort study to estimate rates of histologically confirmed high‐grade cervical abnormality (HGA) and cancer in women with negative Pap smears with and without an ECC. Women 18‐69 years with at least two Pap smears between 1 January 2001 and 31 December 2010 with the first smear in that period (index smear) showing no abnormality were eligible. Follow‐up ended at date of the first abnormal smear, date of histological diagnosis, date of hysterectomy, date of death, or 31 December 2010, whichever came first. ECC status was treated as a time varying exposure. Follow‐up was split at each smear after the index smear. Poisson regression was used to estimate adjusted incidence rates and incidence rate ratios (IRR) by ECC status. The incidence rate of histologically confirmed HGA was significantly lower following ECC− smears than after ECC+ smears (adjusted IRR: 0.69, 95%Confidence Interval (CI) 0.62‐0.77), particularly at older ages (interaction between ECC status and age, p = 0.001). In contrast, the overall rate of invasive cancer was not significantly different after ECC− than after ECC+ smears (IRR: 1.27, 95%CI 0.90‐1.77). In conclusion, women had a lower rate of confirmed HGA and no significant increase in the rate of invasive cervical cancer following ECC− smears. This study does not support differential (accelerated) follow‐up in women with a negative smear without an endocervical component.
Metabolism of Pulmonary Surfactant

Pulmonary surfactant, as isolated by bronchoalveolar lavage from a variety of mammalian species, is a unique mixture of neutral lipids, phospholipids, and at least four surfactant-specific proteins (SP-A, SP-B, SP-C, and SP-D). Its most important, and best characterized, function is maintenance of normal respiratory physiology by mechanical stabilization of the alveolar spaces at low lung volumes and prevention of pulmonary edema. ' An important function more recently elucidated is surfactant's role in host defense mechanisms. Of the proteins, SP-A, SP-B, and SP-C contribute to the surface tension—lowering properties of surfactant, whereas SP-A and SP-D appear important in the host defense function. These compositional and functional variabilities contribute to the inherent complexity of surfactant metabolic processes. Until very recently, studies of surfactant metabolism focused primarily on the major component of surfactant, saturated phosphatidylcholine (PC) or dipalmitoyl phosphatidylcholine (DPPC). Intracellular and extracellular metabolism of this phospholipid by the lung turns out to be very complex. Surfactant is secreted in one form, the lamellar bodies, functions to stabilize the alveoli in another, the monolayer, which is enriched in DPPC, and is taken up into specific cellular compartments, possibly in the form of small vesicles that lack surfactant proteins. Such morphological heterogeneity indicates that form transitions must occur, but there are large gaps in our current konwledge of these events, particularly with respect to regulatory mechanisms responsible for the form transitions. To focus the overall discussion of extracellular and intracellular surfactant component metabolism in the normal lung, this review will use the schematic diagram of pathways for surfactant PC presented in Figure 1, which integrates the work of several investigators. The major metabolic events of synthesis and secretion, extracellular (alveolar) transformations, turnover and recycling, and overall clearance will be used to disorganize the discussion. An attempt is made to synthesize the available data in the literature related to the extracellular transformations that are central to the compositional and metabolic complexity of surfactant. When possible, information from in vitro observations are integrated into the discussion of in vivo measurements that permit us to quantify and track what happens to surfactant following secretion into the complex milieu of the intact lung. Discussion of surfactant proteins is limited to SP-A, SP-B, and SP-C because a role for SP-D is not known.
LC-MS/MS method for the determination of the fungal pigment bikaverin in maize kernels as an indicator of ear rot

Bikaverin is a polyketide-derived pigment produced by multiple species of the fungus Fusarium, some of which can cause ear and kernel rot of maize. A method was developed for the analysis of bikaverin by high-performance liquid chromatography (LC) coupled to electrospray ionisation tandem mass spectrometry (MS/MS). The quantitative nature of the LC-MS/MS method was demonstrated over a range of concentrations of bikaverin in maize. For spike-recovery experiments utilising maize spiked with bikaverin to a level 5 µg g−1 of maize, the measured recovery (%) was 70.6 ± 10.4. Based on the utilised method, the limit of detection (based on a signal-to-noise ratio (S/N) > 3) was better than 0.5 µg g−1 from bikaverin spiked into uncontaminated ground maize. Further, the limit of quantitation (LOQ) was 3 µg g−1 (based on S/N > 10) from bikaverin spiked into ground maize. The method was applied to assess contamination of maize with bikaverin following inoculation of developing maize ears with Fusarium verticillioides under agricultural field conditions.
Fusarium verticillioides from finger millet in Uganda

Finger millet (Eleusine coracana) is a subsistence crop grown in Sub-Saharan Africa and the Indian Sub-continent. Fusarium species occurring on this crop have not been reported. Approximately 13% of the Fusarium isolates recovered from finger millet growing at three different locations in eastern Uganda belong to Fusarium verticillioides, and could produce up to 18,600 µg/g of total fumonisins when cultured under laboratory conditions. These strains are all genetically unique, based on AFLP analyses, and form fertile perithecia when crossed with the standard mating type tester strains for this species. All but one of the strains is female-fertile and mating-type segregates 13:20 Mat-1:Mat-2. Three new sequences of the gene encoding translation elongation factor 1− α were found within the population. These results indicate a potential health risk for infants who consume finger millet gruel as a weaning food, and are consistent with the hypothesis that F. verticillioides originated in Africa and not in the Americas, despite its widespread association with maize grown almost anywhere worldwide.
Robotic Hand–Assisted Training for Spinal Cord Injury Driven by Myoelectric Pattern Recognition: A Case Report

Abstract A 51-year-old man with an incomplete C6 spinal cord injury sustained 26 yrs ago attended twenty 2-hr visits over 10 wks for robot-assisted hand training driven by myoelectric pattern recognition. In each visit, his right hand was assisted to perform motions by an exoskeleton robot, while the robot was triggered by his own motion intentions. The hand robot was designed for this study, which can perform six kinds of motions, including hand closing/opening; thumb, index finger, and middle finger closing/opening; and middle, ring, and little fingers closing/opening. After the training, his grip force increased from 13.5 to 19.6 kg, his pinch force remained the same (5.0 kg), his score of Box and Block test increased from 32 to 39, and his score from the Graded Redefined Assessment of Strength, Sensibility, and Prehension test Part 4.B increased from 22 to 24. He accomplished the tasks in the Graded Redefined Assessment of Strength, Sensibility, and Prehension test Part 4.B 28.8% faster on average. The results demonstrate the feasibility and effectiveness of robot-assisted training driven by myoelectric pattern recognition after spinal cord injury.
Recent developments in molecular sub-typing of Listeria monocytogenes

As a vast majority of the human listeriosis cases are caused by serotypes 1/2a, 1/2b and 4b strains, it is imperative that strains from clinical as well as from food and environment are further characterised so that accurate and timely epidemiological determination of sources of the contamination can be established to minimise the disease burden. Recent developments in the field of genomics provide a great opportunity to use these tools towards the development of molecular sub-typing techniques with a greater degree of discrimination spanning the entire length of the genome. This brief review summarises a few of these DNA-based techniques with an emphasis on DNA microarray and other whole genome sequencing-based approaches and their usefulness in Listeria monocytogenes sub-typing and outbreak investigations.