Miracle-dz/UniFAR-FTUs huggingface dataset:
Automatically diagnosing HER2 amplification status for breast cancer patients using large FISH images

Fluorescence in situ hybridization (FISH) is a technique that prepares acceptable results for molecular imaging biomarkers to precisely and dependably detect and diagnose disorders which are sign of cancers. Since contemporary manual FISH signal analysis is low-effective and inconsistent, it is an attractive research area to develop automated FISH image scanning systems and computer-aided diagnosis (CAD) schemes. The gene expression of epidermal growth factor receptors 2 (HER2) is highly related to results of patients with probable breast cancer. Although FISH technology outperforms other methods, yet it has so many drawbacks. Traditional approaches on FISH analysis are performed manually by clinician. This lets the results are highly dependent to human eye. Also FISH test colors constitutes of dark blue and black regions, it is reasonable that human eye will fail to distinguish between colors. Therefore, the success of computer vision algorithms compared to human eye in analyzing gene expression rate in FISH images will be discussed in this study. Another objective of this study is to expand a CAD program to evaluate HER2 status using acquired images that have MIRAX format. Different large FISH images were chosen for this study from pathology laboratory from Acibadem Maslak hospital. The proposed CAD scheme first applies pre-processing median and gaussian filters. An adaptive thresholding method followed by a watershed segmentation algorithm is employed to segment cells of interest areas. Furthermore, analyzable cells are found and non-detectable cells because of cell overlapping or image staining are discarded. The scheme then splits the detected analyzable region of interest into two red and green color spaces which is also followed by application of a scanning algorithm to detect the CEP17 green and HER2/neu red FISH signals separately. Finally, the proposed method calculates the ratio between independent green and red FISH signals of all analyzable cells identified on the image. The results express that the tool has the ability to automatically express HER2 status using very large FISH images. The results of the computer aided tool would lead to a more effective method in specifying HER2 state of probable patients.
Expression Patterns of Retinoid X Receptors, Retinaldehyde Dehydrogenase, and Peroxisome Proliferator Activated Receptor Gamma in Bovine Preattachment Embryos1

Abstract In cattle, administration of retinol at the time of superovulation has been indirectly associated with enhanced developmental potential of the embryo. Vitamin A and its metabolites influence several developmental processes by interacting with 2 different types of nuclear receptors, retinoic acid receptors and retinoid X receptors (RXRs). Given the limited information available concerning the RXR-mediated retinoid signaling system, particularly in species other than rodents, this study was performed to gain insight into the potential role of retinoid signaling during preattachment embryo development in the cow. Bovine embryos were produced in vitro from oocytes harvested from abattoir ovaries and frozen in liquid nitrogen at the oocyte, 2-, 4-, 8-, and 16- to 20-cell, morula, blastocyst, and hatched blastocyst stages. Reverse transcription polymerase chain reaction (PCR) and whole mount in situ hybridization were utilized to investigate mRNA expression for RXRα, RXRβ, RXRγ, alcohol dehydrogenase I (ADH-I), retinaldehyde dehydrogenase 2 (RALDH2), peroxisome proliferator activated receptor gamma (PPARγ), and glyceraldehyde-3-phosphate dehydrogenase. Transcripts for RXRα, RXRβ, RALDH2, and PPARγ were detected in all stages beginning from the oocyte through to the hatched blastocyst. Whole mount in situ hybridization performed using digoxigenin-labeled antisense probes detected all 4 transcripts in both the inner cell mass and the trophectoderm of hatched blastocysts. PCR products obtained for ADH-I exhibited very low homology to known human and mouse sequences. Immunohistochemistry was performed using polyclonal anti-rabbit antibodies against RXRβ and PPARγ to investigate whether these embryonic mRNAs were translated to the mature protein. Strong immunostaining was observed for both RXRβ and PPARγ in the trophectoderm and inner cell mass cells of intact and hatched blastocysts. Messenger RNA was not detected at any stage for RXRγ. Expression of mRNA for RXRα, RXRβ, RALDH2, and PPARγ suggests that the early embryo may be competent to synthesize retinoic acid and regulate gene expression during preattachment development in vitro.
Dynamic linkages among financial development, economic growth, energy consumption, CO2 emissions and gross fixed capital formation patterns in Malaysia

The aim of this research is to examine the dynamic relationship among financial development, economic growth, energy consumption, CO2 emissions and gross fixed capital formation in Malaysia. Time series data for the period 1970 to 2013, the ARDL model and multivariate Granger causality tests are used to determine the dynamic interrelationship among the study variables. The overall results show: 1) that all the variables are co-integrated during the study period; 2) a long- and short-run relationship existed between energy consumption and economic growth; 3) a long-run unidirectional Granger causality among the study variables is found; 4) there is a bidirectional causality running from economic growth to energy consumption and CO2 emission in the short run. It concludes that, with financial development and economic growth, effective energy policies need to cut the emissions level. The present study may guide the policymakers in formulating proper energy planning in Malaysia to attain future environmental targets while enhancing the financial perspective.
Can a Meta-Analysis Answer the Question: Is Mucosectomy and Handsewn or Double-Stapled Anastomosis Better in Ileal Pouch-Anal Anastomosis?

Although ileal pouch-anal anastomosis (IPAA) is the procedure of choice for polyposis and ulcerative colitis with medically refractory disease or dysplasia, controversy exists concerning whether mucosal preservation with double-stapled (DS) IPAA is superior to mucosectomy and handsewn (HS) IPAA anastomosis for postoperative function. Prospective studies have shown no statistically significant differences. The use of meta-analysis can strengthen statistical power by combining the data from related studies. A meta-analysis was performed to determine whether there was a significant difference in functional and manometric outcome between HS-IPAA and DS-IPAA. Prospective, randomized studies were identified using a literature search. Functional outcome variables included number of normal continence, minor incontinence, nocturnal evacuation, the ability to discriminate flatus from stool, and antidiarrheal medication. Manometric outcomes included postoperative resting and squeeze anal pressures. Four prospective, randomized trials were identified. Of the 184 total patients, the HS-IPAA group included 86 patients (48 men and 38 women) and the DS-IPAA group included 98 patients (49 men and 49 women). There were no significant differences in functional outcome between HS-IPAA and DS-IPAA. In addition, there was no significant difference in sphincter resting and squeeze pressures between the two patient groups. This meta-analysis demonstrates that DS-IPAA offers no advantage in functional or manometric outcome when compared with HS-IPAA.
High frequency of antimicrobial resistance in human fecal flora

The frequency of resistance to seven different antimicrobial agents was examined in the aerobic gram-negative gut flora of over 600 individuals from hospitals, from laboratories where antibiotics were used, and from urban and rural communities. In a majority (62.5%) of fecal samples from people without a recent history of taking antibiotics, 10% or more of the total organisms were resistant to at least one of the antibiotics. In about 40% of the samples, resistance to more than one drug was present at this level. More than one-third of the samples contained resistant organisms comprising 50% or more of the total flora examined. Organisms with coresistance to multiple drugs were found frequently. Individuals taking antibiotics produced more samples with a higher proportion (greater than 50%) of resistant bacteria, and these samples also had a significantly greater number of different resistance determinants. This extensive study revealed a high prevalence of resistant bacteria in the gut flora of ambulatory and hospitalized individuals whether or not they were taking antibiotics.
Involvement of a Novel Efflux System in Biofilm-Specific Resistance to Antibiotics

ABSTRACT Bacteria growing in biofilms are more resistant to antibiotics than their planktonic counterparts. How this transition occurs is unclear, but it is likely there are multiple mechanisms of resistance that act together in order to provide an increased overall level of resistance to the biofilm. We have identified a novel efflux pump in Pseudomonas aeruginosa that is important for biofilm-specific resistance to a subset of antibiotics. Complete deletion of the genes encoding this pump, PA1874 to PA1877 (PA1874-1877) genes, in an P. aeruginosa PA14 background results in an increase in sensitivity to tobramycin, gentamicin, and ciprofloxacin, specifically when this mutant strain is growing in a biofilm. This efflux pump is more highly expressed in biofilm cells than in planktonic cells, providing an explanation for why these genes are important for biofilm but not planktonic resistance to antibiotics. Furthermore, expression of these genes in planktonic cells increases their resistance to antibiotics. We have previously shown that ndvB is important for biofilm-specific resistance (T. F. Mah, B. Pitts, B. Pellock, G. C. Walker, P. S. Stewart, and G. A. O'Toole, Nature 426:306-310, 2003). Our discovery that combining the ndvB mutation with the PA1874-1877 gene deletion results in a mutant strain that is more sensitive to antibiotics than either single mutant strain suggests that ndvB and PA1874-1877 contribute to two different mechanisms of biofilm-specific resistance to antibiotics.
Clinical assessment of diaphragm strength by cervical magnetic stimulation of the phrenic nerves.

BACKGROUND: Accurate assessment of diaphragm strength can be difficult. Transdiaphragmatic pressure (PDI) measurements during volitional manoeuvres are useful but it may be difficult to ensure maximum patient effort. Magnetic stimulation of the phrenic nerves is easy to perform and the results are reproducible in normal subjects. The purpose of the present study was to evaluate the usefulness of magnetic stimulation of the phrenic nerves in the assessment of diaphragm weakness in patients. METHODS: Sixty-six patients referred for assessment of respiratory muscle strength and 23 normal subjects were studied. Twitch PDI (TwPDI) following magnetic stimulation of the phrenic nerves and sniffPDI were obtained in all individuals. TWPDI following bilateral electrical stimulation of the phrenic nerves was also obtained in eight patients. RESULTS: Mean (SD) TwPdi for the normal subjects was 31 (6) cm H2O and 18 (11) cm H2O for the patients. TwPDI and sniffPDI were correlated (r = 0.77). Seven of the 37 patients (19%) with a reduced sniffPDI had a TwPDI within the normal range whereas two of the 32 patients (6%) with a reduced TwPDI had a normal sniffPDI. TwPDI was similar with magnetic and electrical stimulation. CONCLUSIONS: TwPDI following magnetic stimulation of the phrenic nerves is a clinically useful measurement when assessing diaphragm weakness.
Papillomaviruses in non-melanoma skin cancer: epidemiological aspects.

Worldwide, non-melanoma skin cancers (NMSCs), which include squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are the most commonly diagnosed cancers among Caucasians. It is well established that ultraviolet radiation (UVR) plays a central role in the development of these cancers, and more recently, a role for specific genetic mutations in the pathogenesis of BCC has been identified. The possibility that certain types of HPV, either alone or in conjunction with UVR, may play a role in the pathogenesis of these cancers is suggested by several lines of evidence reviewed below. *9 @2depidemiology / non-melanoma skin cancer / papillomavirus
Pharmacotherapy of erectile dysfunction: focus on cardiovascular safety

Therapy of erectile dysfunction has been revolutionised in recent years, as specific pharmacological inhibitors of phosphodiesterase 5 (PDE5), such as sildenafil, tadalafil, or vardenafil, were shown to be highly effective in the treatment of erectile dysfunction. They dilate arterial smooth muscle cells of the corpora cavernosa, which express PDE5 abundantly, by inhibiting the breakdown of 3’5’-cyclic guanosine monophosphate. Despite theoretical concerns of a reduced myocardial tolerance to ischaemia or promoting cardiac arrhythmias, randomised trials and retrospective analyses do not support an increased cardiac risk with oral treatment. Therapeutic doses of PDE 5 inhibitors exhibit slight blood pressure lowering effects, and do not appear to compromise coronary blood flow in coronary artery disease. However, the combination of PDE5 inhibitors with any nitric oxide donor is absolutely contraindicated because of potentially life-threatening hypotension. Before prescribing medication for erectile dysfunction, any patient with cardiovascular disease should be evaluated for a potential risk of a cardiovascular event during sexual activity according to the Princeton Consensus Panel. When a stable cardiac condition can be achieved (low risk group), oral treatment for erectile dysfunction may be appropriate.
Genetic absence of nNOS worsens fetal alcohol effects in mice. I: behavioral deficits.

BACKGROUND Alcohol abuse during pregnancy often induces neuropsychological problems in the offspring, including learning disorders, attention deficits, and behavior problems, all of which are prominent components of fetal alcohol spectrum disorders (FASD). However, not all children who were exposed to alcohol in utero are equally affected by it. While some children have major deficits, others are spared. This unequal vulnerability is likely due largely to differences in fetal genetics. Some fetuses appear to have certain genotypes that make them much more prone to FASD. However, to date, no gene has been identified that worsens alcohol-induced brain dysfunction. Nitric oxide (NO) is a gaseous molecule that can protect developing neurons against alcohol-induced death. In the brain, NO is produced by neuronal nitric oxide synthase (nNOS). In this study, we examined whether homozygous mutation of the nNOS gene in mice worsens the behavioral deficits of developmental alcohol exposure. METHODS Wild-type and nNOS(-/-) mice received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days (PDs) 4 to 9. Beginning on PD 85, the mice underwent a series of behavioral tests, including open field activity, the Morris water maze, and paired pulse inhibition. RESULTS For the wild-type mice, alcohol impaired performance only in the water maze. In contrast, for the nNOS(-/-) mice, alcohol impaired performance on all 3 tasks. Furthermore, the nNOS(-/-) mice were substantially more impaired than wild-type mice in their performance on all 3 of the behavioral tests and at both the low (2.2) and high (4.4) doses of alcohol. CONCLUSIONS Targeted disruption of the nNOS gene worsens the behavioral impact of developmental alcohol exposure and allows alcohol-induced learning problems to emerge that are not seen in wild type. This is the first demonstration that a specific genotype can interact with alcohol to worsen functional brain deficits in an animal model of FASD.
Nerve conduction and biopsy correlation in over 100 consecutive patients with suspected polyneuropathy

Neuropathy was classified physiologically and histologically as normal, axonal, demyelinative, or indeterminate using specific motor nerve conduction (NC) and sural sensory nerve biopsy (NB) criteria. Physiological and histological diagnoses were concordant in 63%, and minimally discordant in 14% of patients. The most important discordant patients were 6 with demyelinative neuropathy, 4 by NC, of which 2 were pure motor syndromes, and 2 by NB, both predominantly sensory syndromes. In the 55 patients with predominant axonal degeneration on biopsy, the extent of NC slowing was determined. As compound motor and sensory nerve action potential (CMAP and SNAP) amplitude declined, distal motor latency increased, whereas motor and sensory conduction velocity (CV) did not. Minimum F response latency increased as motor CV decreased, more in lower than upper extremity nerves. We conclude that: (1) except for sensory neuropathy, routine motor NC studies generally suffice in identifying demyelinative neuropathy; (2) NC slowing in axonal neuropathy is usually slight but may result in significantly prolonged distal motor latencies when CMAP amplitude is very low, and prolonged F wave latency when motor CV is slightly low; and (3) The physiologic criteria employed in this study rarely misclassifies neuropathy as demyelinative in patients with predominant axon loss on biopsy. © 1994 John Wiley & Sons, Inc.
T-2 Toxin/HT-2 Toxin and Ochratoxin A ELISAs Development and In-House Validation in Food in Accordance with Commission Regulation (EU) No 519/2014

T-2 toxin/HT-2 toxin (T-2/HT-2) and ochratoxin A (OTA) are mycotoxins that can contaminate a variety of agricultural commodities. To protect consumers’ health, indicative limits for T-2/HT-2 and maximum limits for OTA have been set by the European Commission, requiring food business operators and controlling agencies to conduct routine checks for the presence of these harmful contaminants. Screening methods are increasingly used for monitoring purposes. Due to the demand for new and improved screening tools, two individual detection methods, T-2/HT-2 and OTA enzyme-linked immunosorbent assays (ELISAs), were developed in this study. The T-2/HT-2 ELISA was based on a T-2 monoclonal antibody with an IC50 (50% inhibitory concentration) of 0.28 ng/mL and 125% cross-reactivity with HT-2. As regards the OTA ELISA, a new sensitive monoclonal antibody specific to OTA with an IC50 of 0.13 ng/mL was produced. Both developed ELISA tests were then validated in agricultural commodities in accordance with the new performance criteria guidelines for the validation of screening methods for mycotoxins included in Commission Regulation (EU) No 519/2014. The T-2/HT-2 ELISA was demonstrated to be suitable for the detection of T-2/HT-2 in cereals and baby food at and above the screening target concentration (STC) of 12.5 μg/kg and 7.5 μg/kg, respectively. The OTA ELISA was shown to be applicable for the detection of OTA in cereals, coffee, cocoa and wine at and above the STC of 2 μg/kg, 2.5 μg/kg, 2.5 μg/kg and 0.4 ng/mL, respectively. The accuracy of both ELISAs was further confirmed by analysing proficiency test and reference samples. The developed methods can be used for sensitive and high-throughput screening for the presence of T-2/HT-2 and OTA in agricultural commodities.
Persistent osteopenia in adult cystic fibrosis transmembrane conductance regulator-deficient mice.

RATIONALE A loss of function mutation in the cystic fibrosis transmembrane conductance regulator gene is believed to be an independent risk factor for bone disease in patients with cystic fibrosis. OBJECTIVES The objective of this work was to use congenic mice as a preclinical model to examine the bone phenotype of Cftr(-/-) mice and control littermates at 8, 12, and 28 weeks of age. METHODS The bone phenotype of control and Cftr(-/-) mice was evaluated by quantitative imaging, histologic and histomorphometric analyses, and serum levels of bone biomarkers. MEASUREMENTS AND MAIN RESULTS At 12 weeks of age, Cftr(-/-) mice were smaller, had lower bone mineral density, cortical bone thinning, and altered trabecular architecture compared with Cftr(+/+) or Cftr(+/-) control mice. In skeletally mature 28-week-old mice, there were persistent deficits in cortical and trabecular bone structure in Cftr(-/-) mice despite significant, quantifiable improvements. Cftr(-/-) mice also had lower serum insulin-like growth factor-I levels at 12 weeks of age than did control mice, whereas parathyroid hormone and 25-hydroxyvitamin D levels were not significantly different. CONCLUSIONS Persistent osteopenia and structural abnormalities in adult Cftr(-/-) mice, in the absence of overt respiratory and gastrointestinal disease, suggest that loss of Cftr function has a direct impact on bone metabolism in Cftr(-/-) mice that is not sex specific or subject to haplotype insufficiency.
Metropolitan endotoxin exposure, allergy and asthma

Purpose of reviewTo review the role of metropolitan endotoxin exposure in asthma and allergy, emphasizing recently published articles (i.e. April 2002-June 2003). Recent findingsIn infants and toddlers in metropolitan communities, higher endotoxin levels in house dust are associated with less atopy and increased wheezing in infancy, but this increased risk may normalize by age 4 years. Increased endotoxin levels and exposure in metropolitan households with dogs and sometimes cats is intriguing in light of recent studies suggesting that animal exposure early in life is associated with less allergen sensitization and asthma. Dust endotoxin also appears to serve as a marker for other similar innate immune-stimulatory microbial components called pathogen-associated molecular patterns. Pathogen-associated molecular patterns, such as bacterial DNA, may augment and steer endotoxin-initiated immune responses in an immune-regulatory direction. These findings support the premise that the differences in health outcomes from endotoxin exposure are due to important moderating variables, such as age of exposure, timing of exposure relative to disease development, dose and frequency of exposure, co-exposures, and genetic predispositions in response to endotoxin. SummaryWe will discuss (1) endotoxin's ability to exacerbate established atopic disease and asthma; (2) factors influencing endotoxin levels in metropolitan homes; (3) relationships between endotoxin, pet exposure, and atopic disease; (4) endotoxin's paradoxical potential to both abrogate as well as exacerbate asthma; and (5) endotoxin's role as a marker for other similar pathogen-associated molecular patterns.
The effects of methane and hydrogen gases produced by enteric bacteria on ileal motility and colonic transit time

Background Gases produced by intestinal flora may modulate intestinal motor function in healthy individuals as well as those with functional bowel disease. Methane, produced by enteric bacteria in the human gut, is associated with slowed intestinal transit and constipation. The effects of hydrogen, another main gas produced by bacterial fermentation in the gut, on small bowel and colonic motor function remains unrecognized. Therefore, we set out to investigate whether intestinal gases including methane and hydrogen could influence the small bowel motility and colonic transit.