Miracle-dz/UniFAR-FTUs huggingface dataset:
Segmented regression, a versatile tool to analyze mRNA levels in relation to DNA copy number aberrations

DNA copy number aberrations (CNA) and subsequent altered gene expression profiles (mRNA levels) are characteristic features of cancerous cells. Integrative genomic analysis aims to identify recurrent CNA that may have a potential role in cancer development, assuming that gene amplification is accompanied by overexpression, while deletions give rise to downregulation of gene expression. We propose a segmented regression‐based approach to identify CNA‐driven alteration of gene expression profiles. Segmented regression allows to fit piecewise linear models in different domains of CNA joined by a change‐point, where the mRNA–CNA relationship undergoes structural changes. Here, we illustrate the implementation and applicability of the proposed model using 1,161 chromosome fragments detected as DNA CNA in primary tumors from 97 breast cancer patients. We identified significant CNA‐driven changes in gene expression levels for 341 chromosome fragments, of which 72 showed a nonlinear relationship to CNA. For 59 of 72 chromosome fragments (82%), we observed an initial increase in mRNA levels due to changes in CNA. After the change‐point was passed, the mRNA levels reached a plateau, and a further increase in DNA copy numbers did not induce further elevation in mRNA levels. In contrast, for 13 chromosome fragments, the change‐point marked the point where mRNA production accelerated. We conclude that segmented regression modeling may provide valuable insights into the impact CNA have on gene expression in cancer cells. © 2011 Wiley Periodicals, Inc.
Functional gain and speech understanding obtained by Vibrant Soundbridge or by open-fit hearing aid

Abstract Conclusion: There is no significant difference in speech recognition scores obtained with the Vibrant Soundbridge and the open-fit hearing aid. However, the Vibrant Soundbridge may be superior to open-fit hearing aids in improving hearing at high frequencies (4–8 kHz). Objectives: To assess whether an improvement in speech recognition conferred by Vibrant Soundbridge is more marked than that afforded by open-fit hearing aids in patients with sloping high frequency sensorineural hearing loss (SNHL). Methods: This study had a self-control prospective design. Seven patients aged 21–62 years with sloping high frequency SNHL were recruited into the study. Each patient received a Vibrant Soundbridge middle ear implant (Vibrant MED-EL) and wore an open-fit hearing aid (Danavox, DOT 10). Speech recognition tests were performed according to protocols suggested by árpád Götze's speech definition test in Hungarian language. In the first session, conventional hearing thresholds (unaided pure tone thresholds) were measured. In the second session, the aided sound-field threshold, speech understanding score and functional gain obtained using middle ear implants and open-fit hearing aids were determined after programming of the devices. Results: Regarding speech recognition scores, there were no significant differences between data obtained with the middle ear implant and those with the open-fit hearing aid.
Modeling susceptibility difference artifacts produced by metallic implants in magnetic resonance imaging with point-based thin-plate spline image registration

Magnetic resonance imaging (MRI) suffers from geometric distortions arising from various sources. One such source are the non-linearities associated with the presence of metallic implants, which can profoundly distort the obtained images. These non-linearities result in pixel shifts and intensity changes in the vicinity of the implant, often precluding any meaningful assessment of the entire image. This work presents a method for correcting these distortions based on non-rigid image registration techniques. Two images from a modelled three-dimensional (3D) grid phantom were subjected to point-based thin-plate spline registration. The reference image (without distortions) was obtained from a grid model including a spherical implant, and the corresponding test image containing the distortions was obtained using previously reported technique for spatial modelling of magnetic susceptibility artifacts. After identifying the nonrecoverable area in the distorted image, the calculated spline model was able to quantitatively account for the distortions, thus facilitating their compensation. Upon the completion of the compensation procedure, the non-recoverable area was removed from the reference image and the latter was compared to the compensated image. Quantitative assessment of the goodness of the proposed compensation technique is presented.
Diagnosis and Management of a Pancreaticopleural Fistula in a Patient with AIDS and a Large Pleural Effusion

Pleural effusions typically present with nonspecific pulmonary complaints in the setting of either acute or chronic diseases. In the general population, these illnesses include congestive heart failure, infection, and malignancy. However, in people living with HIV/AIDS (PLWHA), pleural effusions often result from opportunistic infections and AIDS-defining malignancies, such as Kaposi sarcoma and non-Hodgkin lymphoma. Since the introduction of highly active antiretroviral therapy, there has been a decline in the frequency of AIDS-defining opportunistic infections and AIDS-defining cancers and an increase in certain non-AIDS-defining malignancies including lung cancer. Throughout this period, longer life expectancy in PLWHA has contributed to an increased risk of those chronic diseases that can result in pleural effusions. This case describes an HIV-infected man who was an active cigarette smoker and alcoholic and who presented with a large pleural effusion of uncertain etiology. The authors review several important noncardiac risk factors associated with pleural effusions in PLWHA. The authors also emphasize the importance of obtaining a detailed medical history and the use of appropriate imaging and laboratory tests in order to identify an underlying cause and to provide optimal treatment.
A proposal for the timing of management of patients with melanoma presenting during pregnancy

The treatment of melanoma during and immediately after pregnancy poses a significant challenge to surgeons, oncologists, and patients alike. With the overall increase in incidence of melanoma in the United States and worldwide, it is likely that more surgeons will be faced with management decisions regarding pregnant patients with melanoma. We report on five patients who presented to the Yale Melanoma Unit with melanoma during their pregnancy. We propose the management option of resection of the primary tumor under local anesthesia, and postponing of the sentinel lymph node biopsy until after the birth of the child. The completion lymphadenectomy can be performed if these nodes are found to be harboring metastases. We further discuss treatment options and propose an algorithm for management of patients diagnosed with melanoma while pregnant. J. Surg. Oncol. 2012; 106:36–40. © 2012 Wiley Periodicals, Inc.
Structural biology of tumor necrosis factor demonstrated for undergraduates instruction by computer simulation

This work presents a three‐dimensional (3D) modeling exercise for undergraduate students in chemistry and health sciences disciplines, focusing on a protein‐group linked to immune system regulation. Specifically, the exercise involves molecular modeling and structural analysis of tumor necrosis factor (TNF) proteins, both wild type and mutant. The structure of the tumor necrosis factor type 1 receptor (TNF‐R1) is also briefly explored. TNF and TNF‐R1 play major roles in maintaining human immune‐system homeostasis. Upon binding with TNFR‐1, the TNF can activate the nuclear factor kappa B (NF‐κB), eventually resulting in apoptosis or cell death. These essential features of the clinically relevant TNF family is explored within the frame work of a readily adaptable tutorial. © 2015 by The International Union of Biochemistry and Molecular Biology, 44:246–255, 2016.
State of Investor Sentiment and Aggregate Stock Market Returns

The research literature shows that investor sentiment is a contrarian predictor of aggregate stock market returns; however, we contend that investor sentiment only predicts aggregate stock market returns during high sentiment states where overpricing is more prevalent than underpricing since short-sale restrictions limit the ability of rational investors to exploit overpricing but not underpricing. Using a two-state predictive regression model, we find that investor sentiment indexes of both Baker and Wurgler (2006) and Huang et al. (2014) are contrarian predictor of aggregate stock market returns at all horizons but only during high sentiment states that agrees with our suggestion.
Circadian physiology of metabolism

A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark.
Visually Browsing Millions of Images Using Image Graphs

We present a new approach to visually browse very large sets of untagged images. High quality image features are generated using transformed activations of a convolutional neural network. These features are used to model image similarities, from which a hierarchical image graph is build. We show how such a graph can be constructed efficiently. In our experiments we found best user experience for navigating the graph is achieved by projecting sub-graphs onto a regular 2D image map. This allows users to explore the image collection like an interactive map.
Matrix Metalloproteinase and Tissue Inhibitor of Matrix Metalloproteinase mRNA Levels are Specifically Altered in Torn Rotator Cuff Tendons

Background Rotator cuff tears are a cause of pain and disability in the shoulder. The molecular changes associated with rotator cuff tearing are unclear. A subset of matrix metalloproteinases and tissue inhibitors of metalloproteinase, which are involved in extracellular matrix remodeling and degradation, were evaluated. Hypothesis There would be an increase in the mRNA level of spcific matrix metalloproteinase and a decrease in the mRNA level of specific tissue inhibitors of metalloproteinase in rotator cuff tendon tissue obtained from patients with rotator cuff tears. Study Design Controlled laboratory study. Methods Tissue was obtained from 10 patients undergoing rotator cuff repair for full-thickness rotator cuff tears. Also, tissue was obtained from cadaveric specimens with no gross evidence of rotator cuff tearing. Reverse transcription polymerase chain reaction was performed for the collagenases (MMP-1, MMP-8, MMP-13), the stromelysins (MMP-3, MMP-10, MMP-11), and the tissue inhibitors of metalloproteinase (TIMP-1, TIMP-2, TIMP-3, TIMP-4). Western blotting was performed to confirm the mRNA changes demonstrated in collagenase-3 (MMP-13). Results There was a significant increase in collagenase-3 (MMP-13) mRNA levels, a decrease in stromelysin-1 (MMP-3) mRNA levels, and a decrease in tisue inhibitor of metalloproteinase-2, -3, and -4 mRNA levels. Western blotting demonstrated an increase in the active form of collagenase-3 (MMP-13) in rotator cuff tendon tears. Conclusions The mRNA levels of specific matrix metalloproteinases and tissue inhibitors of metalloproteinase are altered in torn rotator cuff tendons. Clinical Relevance With the known action of the matrix metalloproteinases and tissue inhibitors of metalloproteinase in extra-cellular matrix remodeling, these findings suggest that their roles in remodeling of rotator cuff tears should be further investigated.
The Japanese experience with vaccinating schoolchildren against influenza.

BACKGROUND Influenza epidemics lead to increased mortality, principally among elderly persons and others at high risk, and in most developed countries, influenza-control efforts focus on the vaccination of this group. Japan, however, once based its policy for the control of influenza on the vaccination of schoolchildren. From 1962 to 1987, most Japanese schoolchildren were vaccinated against influenza. For more than a decade, vaccination was mandatory, but the laws were relaxed in 1987 and repealed in 1994; subsequently, vaccination rates dropped to low levels. When most schoolchildren were vaccinated, it is possible that herd immunity against influenza was achieved in Japan. If this was the case, both the incidence of influenza and mortality attributed to influenza should have been reduced among older persons. METHODS We analyzed the monthly rates of death from all causes and death attributed to pneumonia and influenza, as well as census data and statistics on the rates of vaccination for both Japan and the United States from 1949 through 1998. For each winter, we estimated the number of deaths per month in excess of a base-line level, defined as the average death rate in November. RESULTS The excess mortality from pneumonia and influenza and that from all causes were highly correlated in each country. In the United States, these rates were nearly constant over time. With the initiation of the vaccination program for schoolchildren in Japan, excess mortality rates dropped from values three to four times those in the United States to values similar to those in the United States. The vaccination of Japanese children prevented about 37,000 to 49,000 deaths per year, or about 1 death for every 420 children vaccinated. As the vaccination of schoolchildren was discontinued, the excess mortality rates in Japan increased. CONCLUSIONS The effect of influenza on mortality is much greater in Japan than in the United States and can be measured about equally well in terms of deaths from all causes and deaths attributed to pneumonia or influenza. Vaccinating schoolchildren against influenza provides protection and reduces mortality from influenza among older persons.
INFLUENCE OF HYPOXIA AND ADRENALINE ADMINISTRATION ON CORONARY BLOOD FLOW AND CARDIAC PERFORMANCE IN SEAWATER RAINBOW TROUT (ONCORHYNCHUS MYKISS)

To investigate the relationship between cardiac performance and coronary perfusion, cardiovascular variables (Q(dot), Vs, fh, Pda) and coronary blood flow (q·cor) were measured in rainbow trout (Oncorhynchus mykiss) (1.2­1.6 kg) before and after adrenergic stimulation (1.0 µg kg-1 adrenaline) under conditions of (1) normoxia, (2) hypoxia (approximate PwO2 12 kPa) and (3) 2.5 h after returning to normoxia. q·cor for resting fish under normoxic conditions was 0.14±0.02 ml min-1 kg-1 (approximately 0.85 % of Q(dot)). When exposed to hypoxia, although both resting Q(dot) and q·cor increased, q·cor increased to a greater degree (Q(dot) by 17 % and q·cor by 36 %). During hypoxia, maximum adrenaline-stimulated Q(dot) was comparable to that observed for normoxic fish. However, because Q(dot) was elevated in resting hypoxic fish, the capacity of hypoxic fish to increase Q(dot) above resting levels was 50 % lower than that measured in normoxic fish. Although maximum q·cor in adrenaline-injected hypoxic trout was greater than that measured in normoxic trout, post-injection increases in q·cor (above resting levels) were not different between the two groups. Two and a half hours after hypoxic exposure, resting Q(dot) was still elevated (11 %) above normoxic levels, and the ability to increase Q(dot) when adrenergically stimulated was not fully restored. These results suggest (1) that resting q·cor in salmonids is approximately 1 % of Q(dot), (2) that increases in q·cor may be important in maintaining cardiovascular performance during hypoxic conditions, (3) that interactions between alpha-adrenergic constriction and metabolically related vasodilation of the coronary vasculature are important in determining q·cor in fish, (4) that exposure of fish to moderate environmental hypoxia reduces the scope for adrenergically mediated increases in Q(dot), and (5) that periods of recovery in excess of several hours are required before cardiovascular performance returns to pre-hypoxic levels.
Spotlight on naldemedine in the treatment of opioid-induced constipation in adult patients with chronic noncancer pain: design, development, and place in therapy

Opioid-induced constipation (OIC) is an increasingly prevalent problem in the USA due to the growing use of opioids. A novel class of therapeutics, the peripherally acting μ-opioid receptor antagonists (PAMORAs), has been developed to mitigate the deleterious effects of opioids in the gastrointestinal tract while maintaining central analgesia and minimizing opioid withdrawal. This review aimed to summarize the literature on naldemedine, the third PAMORA to gain US Food and Drug Administration (FDA) approval for the treatment of OIC in adults with chronic noncancer pain-related syndromes. Naldemedine has a chemical structure similar to naltrexone, an opioid receptor antagonist, with chemical modifications that limit its ability to cross the blood–brain barrier. Naldemedine was evaluated in two Phase II and three Phase III clinical trials prior to gaining FDA approval. In two pivotal identical Phase III trials, COMPOSE-I (NCT 01965158) and COMPOSE-II (NCT 01993940), patients receiving naldemedine were significantly more likely to respond when compared with placebo (COMPOSE-I: 47.6 vs 34.6%, P=0.002 and COMPOSE-II: 52.5 vs 33.6%, P<0.0001). The most frequent adverse events were abdominal pain (8%) and diarrhea (7%) – rates similar to the other PAMORAs. Based on the available data, naldemedine appears to be an effective and safe drug for the treatment of OIC in adults with chronic noncancer pain.
Sodium channel blockers for neuropathic pain

Importance of the field: The voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability and their abnormal activity is related to several pathological processes, including cardiac arrhythmias, epilepsy, neurodegenerative diseases, spasticity, chronic and neuropathic pain. In particular, neuropathic pain (e.g., postherpetic and trigeminal neuralgia, diabetic neuropathy and spinal cord injury) is a serious clinical problem that affects a high percentage of the world population. Because an altered sodium channel isoform expression profile has been considered one reason for the changes in neuronal excitability, there is a continuous quest for new selective molecules targeting sodium channels for the treatment of chronic pain. Areas covered in this review: PubMed, http://www.sciencedirect. com/, SciFinder® Scholar and http://ep.espacenet. com/ were used as sources for this review and patents between 2007 and September 2009 were taken into account for the sodium channel blockers molecular classes reviewed and discussed herein. What the reader will gain: The sodium channel blockers reported in this review have been categorized into different molecular classes on the basis of their wide structural diversity. This classification, somewhat arbitrary, does not necessarily reflect the presence of pharmacophoric elements but offers a useful way to discuss and comment on structurally homogenous classes of chemotypes recently patented. Take home message: The continuous discoveries in the field of sodium channel blockers, highlighted by the increasing numbers of patent applications published in the last few years and by the numbers of compounds currently in clinical development, underline the importance of this target for the treatment of neuropathic pain. The great difficulty in the design of new selective and active structures, not obtained from old VGSC blockers that are often associated with high risk of adverse effects, is a strong challenge for medicinal chemistry research.
Cytokines and their role in hyperthermia and heat stroke

Abstract Cytokines are intracellular peptides that serve as immune mediators. The levels of both pro- and anti-inflammatory cytokines have been demonstrated to rise in the event of heat stroke in both human and animal models. Different hyperthermic states, including both normal exercise-induced hyperthermia and classical and exertional heat stroke, result in unique characteristic profiles of plasma cytokines. The complexity of the interaction between pro- and anti-inflammatory cytokines is outlined in the vast number of experimental studies and clinical observations reported in the literature. However, there is no unanimous logic in studying the changes in cytokine levels, and therefore, it is difficult to compare the effects seen in the different reports. The strong inflammatory response to heat stroke increases after the cessation of heat stress and is intricately involved both in damage-generating processes and in repair mechanisms that are put into action during the recovery phase. In surviving individuals, this response diminishes in magnitude as time progresses and eventually subsides to allow return-to-normal homeostasis. A greater magnitude of the inflammatory response is often associated with poor prognosis and even fatalities, suggesting an imbalance of the immune system, which causes an unregulated inflammatory response. This review describes the common known processes relating to the predominant cytokines altered in the event of heat injury. The role of cytokines, specifically in the pathophysiology of heat stroke, is elaborated and depicted as part of a biaxial model pertaining to the physiological and cellular/biochemical aspects of heat stroke.
Distensibility of the esophagogastric junction assessed with the functional lumen imaging probe (FLIP™) in achalasia patients

The functional lumen imaging probe (FLIP), measures esophagogastric junction (EGJ) distensibility (cross‐sectional area/luminal pressure) during volume‐controlled distension. The aim of this study is to apply this tool to the assessment of the EGJ in untreated and treated achalasia patients and to compare EGJ distensibility with other diagnostic tools utilized in managing achalasia.
High step-up ratio DC-DC converter using Class-E resonant inverter and Class-DE rectifier for low voltage DC sources

In this paper we propose the study of a Class-E-DE converter circuit which is used in renewable energy electrical power generation systems. The Class-E-DE converter circuit consists of a Class-E resonant inverter and a Class-DE rectifier. This converter is used to convert low voltage DC to high voltage DC and operates on a zero-voltage-switching (ZVS) and low dv/dt mode in order to reduce switching losses at the main switch and the rectifier diode. This converter can increase the output voltage more than older models. The input voltage from the renewable energy source was about 36 V and the output voltage not less than 400 V, the increased output voltage depends on the voltage gain of the circuit. Then, the output voltage of the converter was transferred to the inverter and converted to low frequency AC voltage for the connection to the grid. The converter is important to increase the voltage and efficiency of the grid connection for renewable energy systems. The efficiency of this converter is more than 82% and it operates at a frequency of 1 MHz. The circuit device designed for high density power increased the efficiency of the converter.