Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational Functional Genomics-Based AmpliSeq™ Panel for Next-Generation Sequencing of Key Genes of Pain

The genetic background of pain is becoming increasingly well understood, which opens up possibilities for predicting the individual risk of persistent pain and the use of tailored therapies adapted to the variant pattern of the patient’s pain-relevant genes. The individual variant pattern of pain-relevant genes is accessible via next-generation sequencing, although the analysis of all “pain genes” would be expensive. Here, we report on the development of a cost-effective next generation sequencing-based pain-genotyping assay comprising the development of a customized AmpliSeq™ panel and bioinformatics approaches that condensate the genetic information of pain by identifying the most representative genes. The panel includes 29 key genes that have been shown to cover 70% of the biological functions exerted by a list of 540 so-called “pain genes” derived from transgenic mice experiments. These were supplemented by 43 additional genes that had been independently proposed as relevant for persistent pain. The functional genomics covered by the resulting 72 genes is particularly represented by mitogen-activated protein kinase of extracellular signal-regulated kinase and cytokine production and secretion. The present genotyping assay was established in 61 subjects of Caucasian ethnicity and investigates the functional role of the selected genes in the context of the known genetic architecture of pain without seeking functional associations for pain. The assay identified a total of 691 genetic variants, of which many have reports for a clinical relevance for pain or in another context. The assay is applicable for small to large-scale experimental setups at contemporary genotyping costs.
Evaluation of model compounds–polypropylene film interactions by Fourier transformed infrared spectroscopy (FTIR) method

The interactions of methyl esters, methyl ketones and aldehyde compounds with polypropylene (PP) film were investigated. PP film, placed on a glass vial, was immersed in aqueous solution containing a model flavour compound. After a determined time at 45°C, the PP film was analysed by Fourier transform infrared spectroscopy (FTIR), allowing us to follow the speed of sorption and to quantify its relative rate.
Wireless, soft electronics for rapid, multisensor measurements of hydration levels in healthy and diseased skin

Significance Wireless electronics for monitoring of skin hydration in a quantitative fashion have broad relevance to our understanding of dermatological health and skin structure in both clinical and home settings. Here, we present a miniaturized, long-range automated system that adheres gently to the skin to yield quantitative recordings of skin water content for both epidermis and dermis. This system supports capabilities in characterizing skin barrier, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, with high levels of repeatability and insensitivity to ambient. Benchtop and pilot studies on patients with skin diseases highlight key features of these devices and their potential for broad utility in clinical research and in home settings to guide the management of disorders of the skin. Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.
Prognostic significance of BIRC7/Livin, Bcl-2, p53, Annexin V, PD-L1, DARC, MSH2 and PMS2 in colorectal cancer treated with FOLFOX chemotherapy with or without aspirin

Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatment in vivo in rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p = 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatments in vivo (p <0.05). The mechanistic rational of these effects underscores the importance of expanded concept of possible aspirin combination therapy with FOLFOX sequentially in future CRC management. Validation of our findings through randomized clinical trials of aspirin plus FOLFOX sequentially in patients with CRC is therefore warranted.
Clinically Applicable Quantitative Magnetic Resonance Morphologic Measurements of Grey Matter Changes in the Human Brain

(1) Purpose: Quantitative magnetic resonance imaging (qMRI) measurements can be used to sensitively estimate brain morphological alterations and may support clinical diagnosis of neurodegenerative diseases (ND). We aimed to establish a normative reference database for a clinical applicable quantitative MR morphologic measurement on neurodegenerative changes in patients; (2) Methods: Healthy subjects (HCs, n = 120) with an evenly distribution between 21 to 70 years and amyotrophic lateral sclerosis (ALS) patients (n = 11, mean age = 52.45 ± 6.80 years), as an example of ND patients, underwent magnetic resonance imaging (MRI) examinations under routine diagnostic conditions. Regional cortical thickness (rCTh) in 68 regions of interest (ROIs) and subcortical grey matter volume (SGMV) in 14 ROIs were determined from all subjects by using Computational Anatomy Toolbox. Those derived from HCs were analyzed to determine age-related differences and subsequently used as reference to estimate ALS-related alterations; (3) Results: In HCs, the rCTh (in 49/68 regions) and the SGMV (in 9/14 regions) in elderly subjects were less than those in younger subjects and exhibited negative linear correlations to age (p < 0.0007 for rCTh and p < 0.004 for SGMV). In comparison to age- and sex-matched HCs, the ALS patients revealed significant decreases of rCTh in eight ROIs, majorly located in frontal and temporal lobes; (4) Conclusion: The present study proves an overall grey matter decline with normal ageing as reported previously. The provided reference may be used for detection of grey matter alterations in neurodegenerative diseases that are not apparent in standard MR scans, indicating the potential of using qMRI as an add-on diagnostic tool in a clinical setting.
Engulfed by Glia: Glial Pruning in Development, Function, and Injury across Species

Phagocytic activity of glial cells is essential for proper nervous system sculpting, maintenance of circuitry, and long-term brain health. Glial engulfment of apoptotic cells and superfluous connections ensures that neuronal connections are appropriately refined, while clearance of damaged projections and neurotoxic proteins in the mature brain protects against inflammatory insults. Comparative work across species and cell types in recent years highlights the striking conservation of pathways that govern glial engulfment. Many signaling cascades used during developmental pruning are re-employed in the mature brain to “fine tune” synaptic architecture and even clear neuronal debris following traumatic events. Moreover, the neuron-glia signaling events required to trigger and perform phagocytic responses are impressively conserved between invertebrates and vertebrates. This review offers a compare-and-contrast portrayal of recent findings that underscore the value of investigating glial engulfment mechanisms in a wide range of species and contexts.
A miniature X-ray tube approach to measuring lead in bone using L-XRF

Using a miniature X-ray tube and silicon PiN diode detector, an approach to measuring lead (Pb) in bone phantoms was tested. The X-ray tube was used to excite L-line X-ray fluorescence (L-XRF) of lead in bone phantoms. The bone phantoms were made from plaster of Paris and dosed with varying quantities of lead. Phantoms were made in two sets with different shapes to model different bone surfaces. One set of bone phantoms was circular in cross-section (2.5-cm diameter), the other square in cross-section (2.2 cm × 2.2 cm). Using an irradiation time of 180 s (real time), five trials were run for each bone phantom. Analysis was performed for both Lα and Lβ lead X-rays. Based on these calibration trials, (3σ0/slope) minimum detection limits of 7.4 ± 0.3 µg Pb g−1 (circular cross-section) and 8.6 ± 0.6 µg Pb g−1 (square cross-section) were determined for the bare bone phantoms. To simulate a more realistic in vivo scenario with soft tissue overlying bone, further trials were performed with a resin material placed between the experimental system and the bone phantom. For the square cross-section bone phantoms, a layer of resin with a thickness of 1.2 mm was used, and a minimum detection limit of 17 ± 3 µg Pb g−1 determined. For the circular cross-section phantoms, a layer of resin with an average thickness of 2.7 mm was used. From these, a more realistic minimum detection limit for in vivo applications (43 ± 7 µg Pb g−1) was determined. Copyright © 2011 John Wiley & Sons, Ltd.
Adenomyotic cyst mimicking a congenital Müllerian anomaly: Diagnosis and treatment with laparoscopy

A 28-year-old woman presented with a 1-year history of severe progressive dysmenorrhea following suction evacuation and tubal ligation. Sonography showed a bicornuate uterus with hematometra in the left horn. Hysteroscopy ruled out a diagnosis of a congenital Müllerian anomaly, as both ostia appeared normal. Under laparoscopy, a mass was seen on the left fundal region near the insertion of the round ligament, and needle aspiration of a chocolate-colored fluid confirmed the diagnosis of an adenomyotic cyst. The cyst was excised. The patient recovered well and has been symptom-free since surgery. Adenomyotic cyst is a rare entity in young women and must be differentiated from obstructive Müllerian anomaly. Laparoscopy is the preferred minimally invasive modality for managing this rare disorder.
The Combined Effects of Magnesium Oxide and Inulin on Intestinal Microbiota and Cecal Short-Chain Fatty Acids

Constipation is a common condition that occurs in many people worldwide. While magnesium oxide (MgO) is often used as the first-line drug for chronic constipation in Japan, dietary fiber intake is also recommended. Dietary fiber is fermented by microbiota to produce short-chain fatty acids (SCFAs). SCFAs are involved in regulating systemic physiological functions and circadian rhythm. We examined the effect of combining MgO and the water-soluble dietary fiber, inulin, on cecal SCFA concentration and microbiota in mice. We also examined the MgO administration timing effect on cecal SCFAs. The cecal SCFA concentrations were measured by gas chromatography, and the microbiota was determined using next-generation sequencing. Inulin intake decreased cecal pH and increased cecal SCFA concentrations while combining MgO increased the cecal pH lowered by inulin and decreased the cecal SCFA concentrations elevated by inulin. When inulin and MgO were combined, significant changes in the microbiota composition were observed compared with inulin alone. The MgO effect on the cecal acetic acid concentration was less when administered at ZT12 than at ZT0. In conclusion, this study suggests that MgO affects cecal SCFA and microbiota during inulin feeding, and the effect on acetic acid concentration is time-dependent.
Immunotoxicity of environmentally relevant mixtures of polychlorinated aromatic hydrocarbons with methyl mercury on rat lymphocytes in vitro

The immunosuppressive effects of methyl mercury (MH), polychlorinated biphenyls (PCBs), polychlorinated dibenzo‐p‐dioxins (PCDDs), and dibenzofurans (PCDFs) are well established at high exposure levels but unclear at low exposure levels. We exposed Fischer 344 rat splenocytes, thymocytes, and peripheral blood lymphocytes in vitro for 72 h to MHg (0.1, 2 μg/ml), PCDD/PCDF mixtures (1, 15 pg/ml) of three PCDDs (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin, 1,2,3,7,8‐pentachlorodibenzo‐p‐dioxin, and 1,2,3,4,7,8‐hexachlorodibenzo‐p‐dioxin) and two PCDFs (2,3,7,8‐tetrachlorodibenzofuran and 1,2,3,7,8‐pentachlorodibenzo‐furan), three Aroclor® (1242, 1254, 1260), PCB mixtures (0.01, 0.5 μg/ml), or combinations of MHg/PCB/PCDD/PCDF mixtures Mitogenic responses of lymphocytes to concanavalin A, phytohemagglutinin, or lipopolysaccharide/dextran sulfate were determined by 3H‐thymidine uptake; cytotoxicity and intracellular Ca2+ were determined by flow cytometry. Methylmercury (2 μg/ml and PCB/ PCDD/PCDF mixtures with 2 μg/ml MHg decreased the viability of splenocytes to 57 and 40% at 4 and 24 h, respectively. Basal intracellular calcium ion levels were unaffected by the treatments. Methylmercury suppressed the responses of lymphocytes to T and B cell mitogens. All combinations of MHg/PCB/PCDD/PCDF mixtures decreased mitogenic responses to levels similar to those to MHg alone. In contrast, PCB and PCDD/PCDF mixtures did not suppress but augmented responses of splenocytes and peripheral blood lymphocytes to T cell mitogens. Overall, no interactive toxicity was observed with MHg/PCB/PCDD/PCDF mixtures on cytotoxicity and lymphocyte mitogenic responses. Therefore, MHg may pose a greater threat than organochlorines to the mammalian immune system.
Novel Sorbents For Mercury Removal From Flue Gas

A laboratory-scale packed-bed reactor system is used to screen sorbents for their capability to remove elemental mercury from various carrier gases. When the carrier gas is argon, an on-line atomic fluorescence spectrophotometer (AFS), used in a continuous mode, monitors the elemental mercury concentration in the inlet and outlet streams of the packed-bed reactor. The mercury concentration in the reactor inlet gas and the reactor temperature are held constant during a test. For more complex carrier gases, the capacity is determined off-line by analyzing the spent sorbent with either a cold vapor atomic absorption spectrophotometer (CVAAS) or an inductively coupled argon plasma atomic emission spectrophotometer (ICP-AES). The capacities and breakthrough times of several commercially available activated carbons as well as novel sorbents were determined as a function of various parameters. The mechanisms of mercury removal by the sorbents are suggested by combining the results of the packed-bed testing with .
Endovascular treatment of trigeminal neuralgia with cranial autonomic symptoms due to a right-sided petrous ridge dAVF

Abstract Dural arteriovenous fistula represents a rare cause of secondary Trigeminal Neuralgia. To date, there have been 18 reported cases of successful treatment of trigeminal neuralgia with endovascular embolization. Here we describe a unique case of a 51-year-old man with right-sided petrous ridge dural arteriovenous fistula causing ipsilateral V1 pain and cranial autonomic dysfunction. Cerebral angiography confirmed a Cognard type 3 right-sided tentorial dAVF supplied by an enlarged meningo-hypophpyseal vessel from the extradural ICA and by the middle meningeal artery. The fistula drains towards the midline via deep cerebral veins, the internal cerebral vein and the straight sinus with likely variceal compression of the right trigeminal nerve root entry zone. Transarterial Onyx embolization resulted in complete obliteration of the dural arteriovenous fistula with immediate resolution of facial pain and autonomic symptoms. After 24 months, the patient remains symptom-free and has no radiographic or clinical evidence of fistula recurrence. To date, there have been no other cases reported of trigeminal neuralgia with cranial autonomic symptoms or SUNCT syndrome due to a dural arteriovenous fistula. The presence of cranial autonomic symptoms with trigeminal neuralgia or a diagnosis of SUNCT should not deter endovascular treatments of dural arteriovenous fistulas or treatment of other compressive vascular lesions.
Association between Dog Owner Demographics and Decision to Seek Veterinary Care

(1) Background: An important aspect of dog ownership is providing veterinary care. However, features of dog ownership differ across demographic groups and these may influence veterinary client decision making and behavior. The purpose of the present study was to elucidate relationships between American dog owner characteristics and willingness to seek veterinary care. (2) Methods: A total of 858 dog owners completed an online questionnaire asking participants to rate their level of likelihood to seek veterinary care for different medical conditions, answer supplemental questions about their previous veterinary barriers, and indicate barriers that prevent them from seeking veterinary care. (3) Results: Dog owners did not differ by demographics in their willingness to seek veterinary care. However, dog owner demographic groups varied in their relationship with their dog(s), previous behaviors accessing veterinary care, and barriers that make seeking veterinary care challenging. (4) Conclusions: Education, outreach and community-based veterinary medicine efforts should allocate resources to underserved communities identified within the context that they are affected by barriers to obtaining veterinary care for their dog(s).
Band engineering of high performance p-type FeNbSb based half-Heusler thermoelectric materials for figure of merit zT > 1

We report new p-type FeNb1−xTixSb (0.04 ≤ x ≤ 0.24) half-Heusler thermoelectric materials with a maximum zT of 1.1 at 1100 K, which is twice that of the ZrCoSb half-Heusler alloys. The electrical properties are optimized by a tradeoff between the band effective mass and mobility via a band engineering approach. A high content of Ti up to x = 0.2 optimizes the power factor and reduces the lattice thermal conductivity. In view of abundantly available elements, good stability and high zT, FeNb1−xTixSb alloys could be promising materials for high temperature power generation.
Magnetic and other studies of ruthenium dioxide and its hydrate

The magnetic behaviour of ruthenium dioxide up to 1000°K is interpreted in terms of J being ca. – 3000 cm. –1 in dioxo-bridged chains of ruthenium atoms. The high electrical conductivity as well as certain structural features imply that the average oxidation state of the ruthenium atoms is substantially greater than +4.The oxide hydrate has a high surface area; it is formulated as RuO2 +x, yH2O since there can be an excess (chemisorbed) of oxygen particularly after removal of some of the water. Values of x up to 0·12 have been found whereas y is often 1 to 1·3. The susceptibility, though generally similar to that of RuO2, varies from sample to sample: its behaviour is discussed in relation both to the influence of adsorbed groups and also to some terminal ruthenium atoms behaving as mononuclear Ru(V), i.e., being in the d3 state. Expected spectral bands in the infrared have not been detected owing to the presence of electronic conductance bands.