Miracle-dz/UniFAR-FTUs huggingface dataset:
Intra-tumoral heterogeneity in the expression of programmed-death (PD) ligands in isogeneic primary and metastatic lung cancer: Implications for immunotherapy

ABSTRACT Purpose: There is inconclusive evidence to suggest the expression of programmed cell death (PD) ligand 1 (PD-L1) is a putative predictor of response to PD-1/PD-L1-targeted therapies in lung cancer. We evaluated the heterogeneity in the expression of PD-1 ligands in isogeneic primary and metastatic LC specimens. Experimental Design: From 12,580 post mortem cases, we identified 214 patients with untreated metastatic LC, of which 98 had adequately preserved tissues to construct a syngeneic primary LC/metastasis tissue microarray. Immunostaining for PD-L1 and 2 was evaluated in paired primary and metastatic lesions and correlated with clinicopathologic features. Results: We included 98 patients with non-small cell (NSCLC, n = 65, 66%), small cell histology (SCLC, n = 29, 30%) and four (4%) atypical carcinoids (AC). In total 8/65 (12%) primary PD-L1 positive NSCLC, had discordant matched metastases (14/17, 82%). PD-L1 negative primaries had universally concordant distant metastases. SCLCs were universally PD-L1 negative across primary and metastatic disease. PD-L2 positive NSCLC (n = 11/65, 17%) had high rate of discordant metastases (n = 24/27, 88%) and four cases (6%) had PD-L2 positive metastases with negative primaries. 2/29 SCLC (7%) and 1/4 AC (25%) were PD-L2 positive with discordance in all the sampled metastatic sites (n = 5). We found no correlation between the expression of PD ligands and clinicopathologic features of LC. Conclusions: Intra-tumoral heterogeneity in the expression of PD ligands is common in NSCLC, while PD-L1 is homogeneously undetectable in primary and metastatic SCLC. This holds implications in the clinical development of immune response biomarkers in LC.
Delayed Postnatal Development of NMDA Receptor Function in Medium-Sized Neurons of the Rat Striatum

During early postnatal development, the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays a dominant role in excitatory amino acid-mediated synaptic transmission in essentially every brain region that has been examined. In contrast, we have found that in the rat striatum, NMDA receptor-mediated current develops later in the medium-sized neurons (MSNs) than currents mediated by activation of non-NMDA receptors. MSNs were identified using infrared video microscopy, and voltage-clamped in a slice preparation using the whole-cell patch-clamp technique. Intrastriatal stimulation was used to evoke excitatory synaptic currents from slices in animals ranging in age from postnatal day (PND) 5 to 60. Though most cells from animals younger than PND 10 failed to respond to synaptic stimulation, postsynaptic responses were occasionally evoked in cells as young as PND 5. Synaptic currents from cells between PNDs 5 and 7 had a significant contribution due to activation of non- NMDA receptors, as evidenced by sensitivity to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and rapidly rising and falling response components. The relative contribution of NMDA receptors increased approximately twofold from the first to the third postnatal week; no further change was observed through PND 60. At the same ages that the NMDA receptors contributed maximally to the synaptic current, the decay time constant of the NMDA receptor-mediated current decreased significantly. The increasing weight of NMDA receptor-mediated current may reflect a change in the number of functional receptors at the synapse since there was no apparent change in the voltage dependence of the current. To more completely examine receptor function early in postnatal development, NMDA and kainate were applied either iontophoretically or in the bath. Iontophoretic application of NMDA onto cells obtained from rats between PNDs 3 and 5 only occasionally evoked current, provided that the membrane was held at depolarized potentials to remove the Mg2+ block. In contrast, application of kainate consistently evoked a response from cells of the same age group. Bath application of the same agonists provided similar results. Taken together, the present experiments demonstrate that striatal non-NMDA receptor-mediated currents are more mature than NMDA receptor-mediated currents early in development.
Clinical assessment of noninvasive intracranial pressure absolute value measurement method

Objective: To assess prospectively the accuracy and precision of a method for noninvasive intracranial pressure (ICP) measurement compared with invasive gold standard CSF pressure measurement. Methods: Included were 62 neurologic patients (37 idiopathic intracranial hypertension, 20 multiple sclerosis, 1 Guillain-Barré syndrome, 1 polyneuropathy, and 3 hydrocephalus). The average age was 40 ± 12 years. All patients had lumbar puncture indicated as a diagnostic procedure. ICP was measured using a noninvasive ICP measurement method, which is based on a two-depth high-resolution transcranial Doppler insonation of the ophthalmic artery (OA). The OA is being used as a natural pair of scales, in which the intracranial segment of the OA is compressed by ICP and the extracranial segment of the OA is compressed by extracranial pressure (Pe) applied to the orbit. The blood flow parameters in both OA segments are approximately the same in the scales balance case when Pe = ICP. All patients had simultaneous recording of noninvasive ICP values and invasive gold standard CSF pressure values. Results: Analysis of the 72 simultaneous paired recordings of noninvasive ICP and the gold standard CSF pressure showed good accuracy for the noninvasive method as indicated by the low mean systematic error (0.12 mm Hg; confidence level [CL] 0.98). The method also showed high precision as indicated by the low SD of the paired recordings (2.19 mm Hg; CL 0.98). The method does not need calibration. Conclusion: The proposed noninvasive ICP measurement method is precise and accurate compared with gold standard CSF pressure measured via lumbar puncture.
Ultra high-performance ASIC implementation of SM2 with power-analysis resistance

In this paper, we propose a high-performance implementation of elliptic curve cryptography over SCA-256 prime field by introducing an all-new isochronous architecture, which can also resist power-analysis attack. By modifying Montgomery ladder-based scalar multiplication, point addition (PA) and point double (PD) can operate synchronously, resisting simple power analysis (SPA) and double attack with minimum time-cost. Then PA and PD are designed to be strictly isochronous units by matching our configurable modular multiplication unit of pipelined stage. Both algorithm and hardware schedule are optimized from bottom to up, random cycles are also inserted to resist differential power analysis (DPA). In the hardware evaluation using CMOS standard cell library of 0. 13μm, our ECC processor achieves 211μs and 8. 5μJ for one scalar multiplication with 208k gate counts. Compared to other related designs, our architecture offers not only 2~6 times better area-time product but also great power-analysis resistance.
Gray matter changes related to medication overuse in patients with chronic migraine

Objective The objective of this article is to investigate the neurological substrates associated with medication overuse (MO) in patients with chronic migraine (CM). Methods We recruited age- and sex-matched CM patients with MO (CMwMO), CM patients without MO (CMwoMO), and healthy controls (HCs). Magnetic resonance T1-weighted images were processed by voxel-based morphometry, and the findings were correlated with clinical variables and treatment responses. Results A total of 66 patients with CM (half with MO) and 33 HCs completed the study. Patients with CMwMO compared to the patients with CMwoMO showed gray matter volume (GMV) decrease in the orbitofrontal cortex and left middle occipital gyrus as well as GMV increase in the left temporal pole/parahippocampus. The GMV changes explained 31.1% variance of the analgesics use frequency. The patients who responded to treatment had greater GMV in the orbitofrontal cortex (p = 0.028). Patients with CM (with and without MO), compared with HCs, had decreased GMV at multiple brain areas including the frontal, temporal and occipital lobes, precuneus and cerebellum. Conclusions Our study showed GMV changes in CMwMO patients compared to the CMwoMO patients. These three cerebral regions accounted for significant variance in analgesics use frequency. Moreover, the GMV of the orbitofrontal cortex was predictive of the response to MO treatments.
Intraocular Neovascularization Associated with Choroidal Ganglioneuroma in Neurofibromatosis Type 1

Purpose. Neurofibromatosis type 1 (NF-1) complicates various tumors originating from the neural crest. The authors report a case of NF-1 presenting with globe enlargement and subretinal and choroidal neovascularization associated with choroidal ganglioneuroma. Methods. A 7-year-old boy with NF-1 had severe ocular pain OS. He has a medical history of congenital glaucoma OS. Left eye showed increased intraocular pressure, buphthalmos, corneal opacity, hyphema, and vitreous hemorrhage. Magnetic resonance imaging indicated prominent vitreous hemorrhage and a choroidal tumor. Enucleation was consequently performed OS. Results. Histopathologic diagnosis of the choroidal tumor was ganglioneuroma admixed with micro-vessels and melanocytes. There was a huge subretinal and choroidal fibrovascular membrane formation originating from the choroidal ganglioneuroma. Conclusions. Severe ocular pain in this patient was caused by intraocular neovascularization and subsequent increased eyeball content by vitreous hemorrhage associated with the choroidal tumor. In NF-1 with orbitofacial involvement, detection of intraocular tumor by imaging tests may predict tumor-associated severe ophthalmic complications.
Parasite Assemblages of Australian Species of Pseudomys (Rodentia: Muridae: Murinae)

abstract: The parasite fauna of many Australian rodents is poorly known. The ectoparasite and helminth faunas of Pseudomys delicatulus, Pseudomys desertor, Pseudomys gracilicaudatus, and Pseudomys hermannsburgensis were determined and compared. In total, 12 species of arthropods, 2 cestodes, and 13 nematodes were found. Species richness of parasites was highest in P. hermannsburgensis and lowest in P. desertor. Despite the sampling effort, the number of parasite species discovered did not reach an asymptote for any of the host species, indicating that the full parasite fauna was not examined. Helminth species richness was highest in the insectivorous P. hermannsburgensis and lower in the obligate herbivores. The structure of parasite component communities was influenced by the social structure of the host species, not surprisingly, with the most highly social species having the highest richness of parasites. Habitat preferences also provided contrast between the helminth component communities, with heligmonellid nematodes occurring in damp woodlands and dominating the parasite fauna of P. gracilicaudatus. Oxyurid nematodes dominated the component communities of the 3 other species, all of which inhabit drier habitats.
Bilateral parotid gland enlargement and hyperlipoproteinemia.

Sjogren's syndrome was the initial diagnosis of the physicians who referred five patients with bilateral, noninflammatory parotid gland enlargement. This diagnosis was not confirmed in any case. All five patients had elevated plasma triglyceride concentrations and mild diastolic hypertension. Increased intake of alcoholic beverages, abnormal glucose tolerance, and moderate obesity were frequently present. Massive replacement of the parotid gland tissue by fat was observed in two biopsy specimens. Restriction of calories, alcoholic beverages, and the percent of calories from carbohydrate resulted in regression of parotid gland size in three patients observed for more than three months. A modest short-term reduction in size of the parotid gland occurred in one other patient over a five-week period. Hypertriglyceridemia was also ameliorated by this dietary regimen.
Immunohistochemical detection of the multidrug transport protein P1 70 in human normal tissues and malignant lymphomas

Two monoclonal antibodies, MRK16 and C219, both directed at the 170 kDa P‐glycoprotein multidrug resistance agent, were applied to frozen sections or cytospin preparations from normal human tissues and 60 non‐Hodgkin's malignant lymphomas. Adrenal gland, kidney, liver and pancreas were always stained by the reagents, albeit with slightly different patterns. Brain capillaries as well as macrophages and some elements of the bone marrow, peripheral blood, ovarian stroma and colonic, gastric and jejunal mucosa were positive in all examined preparations. There were differences in the staining patterns with the two antibodies. Among the 60 non‐Hodgkin's lymphomas, 25 contained a number of positive cells, which ranged from 2% to 100%. No correlation was seen between the expression of P1 70 and histological type, stage, clinical symptoms or growth fraction. A close relationship was shown between the presence of P1 70 positive elements and the clinical course of the disease (P<0.001).
Ankle brachial index <0.9 underestimates the prevalence of peripheral artery occlusive disease assessed with whole-body magnetic resonance angiography in the elderly

Background: Whole-body magnetic resonance angiography (WBMRA) permits noninvasive vascular assessment, which can be utilized in epidemiological studies. Purpose: To assess the relation between a low ankle brachial index (ABI) and high-grade stenoses in the pelvic and leg arteries in the elderly. Material and Methods: WBMRA was performed in a population sample of 306 subjects aged 70 years. The arteries below the aortic bifurcation were graded after the most severe stenosis according to one of three grades: 0–49% stenosis, 50–99% stenosis, or occlusion. ABI was calculated for each side. Results: There were assessable WBMRA and ABI examinations in 268 (right side), 265 (left side), and 258 cases (both sides). At least one ⩾50% stenosis was found in 19% (right side), 23% (left side), and 28% (on at least one side) of the cases. The corresponding prevalences for ABI <0.9 were 4.5%, 4.2%, and 6.6%. An ABI cut-off value of 0.9 resulted in a sensitivity, specificity, and positive and negative predictive value of 20%, 99%, 83%, and 84% on the right side, and 15%, 99%, 82%, and 80% on the left side, respectively, for the presence of a ⩾50% stenosis in the pelvic or leg arteries. Conclusion: An ABI <0.9 underestimates the prevalence of peripheral arterial occlusive disease in the general elderly population.
Using Single-System Analyses to Assess the Effectiveness of an Exercise Intervention on Quality of Life for Hispanic Breast Cancer Survivors: A Pilot Study

ABSTRACT Stress is associated with many health maladies, including cancers. Exercise is an effective stress-management tool and is important for physical health. The number of Hispanic women who engage in enough exercise is low. Thus, promoting exercise for this population is of critical importance. Individual effectiveness of behavioral interventions can often be lost in group analyses. Therefore, we employed both group analyses and single-system methodology to test the effectiveness of an exercise program for 25 Hispanic breast cancer survivors. Measures of physical fitness, quality of life, self-reported stress, and salivary cortisol were taken repeatedly before, during, and after the intervention. The intervention improved physical fitness, reduced perceived stress, and decreased cortisol levels as evidenced by both group and single-system analyses.
Trends in self-rated health in European and North-American adolescents from 2002 to 2010 in 32 countries.

BACKGROUND Self-rated health (SRH) in adolescence is known to be associated with health outcomes in later life. We carried out a trend analysis on data coming from three waves of data collected in 32 countries (mostly European) from 2002 to 2010 coming from the Health Behaviour in School-Aged Children surveys. METHODS SRH in adolescents was assessed using a Likert scale (excellent, good, fair and poor). Responses were dichotomized into 'excellent' vs. 'rest'. Country, age and gender groups were compared based on the odds ratio of declaring excellent SRH in 2010 with respect to 2002 and 2006. RESULTS The trend for European adolescents indicates an improvement over the last decade, although, in the majority of countries, a higher proportion of adolescents rate their health as excellent during the period 2002-06 with respect to the second half of the decade (2006-10). Girls were found to constantly rate their health as poorer, compared to their male peers, in all countries. Age has also a very stable trend towards a decreasing rating of health with increasing age. CONCLUSION Decreased rating of health in the period 2006-10 may be a signal of the socio-economic difficulties of Europe in the last part of this decade.
Assessment of stress levels among cats in four animal shelters.

OBJECTIVE To measure stress levels among cats in traditional and enriched shelter environments via behavioral assessment and urine cortisol-to-creatinine ratios. DESIGN Cross-sectional observational study. ANIMALS 120 cats in 4 Boston-area animal shelters. PROCEDURE Cats were randomly selected and observed during 3 periods (morning, midday, and afternoon) of 1 day and scored by use of a behavioral assessment scale. The next day, urine samples were collected for analysis of the urine cortisol-to-creatinine ratio. Information about each cat's background before entering the shelter was collected. RESULTS Stress scores were highest in the morning. The relationships between the amount of time cats spent in the shelter and the cat stress score or urine cortisol-to-creatinine ratio were not strong. There was no correlation between the cat stress score and urine cortisol-to-creatinine ratio. Urine cortisol-to-creatinine ratios did correlate with signs of systemic disease and were significantly lower in cats in the more environmentally enriched shelters, compared with cats in the traditional shelters. Urine cortisol-to-creatinine ratio was highest among cats with high exposure to dogs. Of the cats in the study, 25% had subclinical hematuria detectable on a urine dipstick. CONCLUSIONS AND CLINICAL RELEVANCE In this study, the cat stress score was not a useful instrument for measuring stress because it failed to identify cats with feigned sleep and high stress levels. Urine cortisol-to-creatinine ratios can be monitored to noninvasively assess stress levels in confined cats. Environmental enrichment strategies may help improve the welfare of cats in animal shelters.
Survival Skills for the IS Professional

IS professionals can only dream of the days when technical brilliance alone was enough to ensure a successful career. Now business acumen and a strong understanding of customer expectations are vital to long-term career survival. Based on their study of 75 experienced IS professionals, the authors present guidelines for fostering the development of customer-oriented IS professionals.
Prostate hyperplasia caused by long‐term obesity is characterized by high deposition of extracellular matrix and increased content of MMP‐9 and VEGF

Recent studies have shown a positive association of cancer and obesity, but the morphological and molecular mechanisms involved in this relationship are still unknown. This study analysed the impact of long‐term obesity on rat prostate, focusing on stromal changes. Male adult Wistar rats were treated with high‐fat diet to induce obesity, while the control group received a balanced diet. After 30 weeks of feeding, the ventral prostate was analysed by immunohistochemistry for cell proliferation, smooth muscle α‐actin, vimentin, chondroitin sulphate and metalloproteinases (MMP‐2 and 9). The content of androgen receptor (AR), oestrogen receptors (ERs) and vascular endothelial growth factor (VEGF) was measured by Western blotting, and activity of catalase and Glutathione‐S‐Transferase (GST) were quantified by enzymatic assay. Long‐term obesity decreased testosterone plasma levels by 70% and resulted in stromal prostate hyperplasia, as evidenced by increased collagen fibres. Such stromal hyperplasia was associated with increased number of blood vessels and raised VEGF content, and increased expression of chondroitin sulphate, vimentin, α‐actin and MMP‐9. In spite of the high cell density in prostate, the proliferative activity was lower in the prostates of obese rats, indicating that hyperplasia was established during the early phases in this obesity model. AR levels increased significantly, whereas the ERα decreased in this group. Moreover, the levels of catalase and GST were changed considerably. These findings indicate that long‐term obesity, besides disturbing the antioxidant control, causes intense stromal remodelling and release of factors that create an environment that can promote proliferative disorders in the gland, culminating with diffuse hyperplasia.
Optimising use of thiopurines in inflammatory bowel disease

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are the most widely used immunosuppressive therapies in inflammatory bowel disease. Pretreatment measurement of thiopurine methyltransferase (TPMT) activity is recommended and although conventional practice is to use a dose of 2 mg/kg AZA (1 mg/kg 6-MP), higher doses of 2.5 mg/kg AZA or more may be required in some patients, particularly if TPMT activity is high. Dose raising is limited by toxicity, and a robust monitoring system is mandatory. Patients with side effects to AZA may tolerate 6-MP but pancreatitis is a contraindication to switching. Metabolite monitoring is not widely available but may be useful, particularly if non-compliance is possible or where metabolite shunting to 6-methylmercaptopurine is suspected, on the basis of non-response or toxicity. It may allow dose optimisation before switching to alternative immunosuppressants. The drug appears safe in pregnancy and breast feeding. Long term duration of therapy is a balance between benefits in relation to the underlying disease extent, activity and aggressiveness, and the risk of neoplasia, particularly lymphoma.
Revisions to the JDL data fusion model

The Data Fusion Model maintained by the Joint Directors of Laboratories (JDL) Data Fusion Group is the most widely-used method for categorizing data fusion-related functions. This paper discusses the current effort to revise the expand this model to facilitate the cost-effective development, acquisition, integration and operation of multi- sensor/multi-source systems. Data fusion involves combining information - in the broadest sense - to estimate or predict the state of some aspect of the universe. These may be represented in terms of attributive and relational states. If the job is to estimate the state of a people, it can be useful to include consideration of informational and perceptual states in addition to the physical state. Developing cost-effective multi-source information systems requires a method for specifying data fusion processing and control functions, interfaces, and associate databases. The lack of common engineering standards for data fusion systems has been a major impediment to integration and re-use of available technology: current developments do not lend themselves to objective evaluation, comparison or re-use. This paper reports on proposed revisions and expansions of the JDL Data FUsion model to remedy some of these deficiencies. This involves broadening the functional model and related taxonomy beyond the original military focus, and integrating the Data Fusion Tree Architecture model for system description, design and development.