Miracle-dz/UniFAR-FTUs huggingface dataset:
Cysteine protease activity is up-regulated in inflamed ankle joints of rats with adjuvant-induced arthritis and decreases with in vivo administration of a vinyl sulfone cysteine protease inhibitor.

OBJECTIVE Cysteine proteases are postulated to play a role in tissue destruction in the joints of animals with arthritis. The purpose of the present study was to confirm the concept that cysteine proteases are enzymes involved in the pathology of rheumatoid arthritis (RA). METHODS Arthritis was induced in Lewis rats by adjuvant injection (adjuvant-induced arthritis [AIA] model) and scored for inflammation. At necropsy, the rear paws were either fixed in formalin and assigned a histologic score (based on synovial cell proliferation, cartilage erosion, bone erosion, and fibroproliferative pannus) or frozen, cryosectioned, and assayed for enzyme activity either by in situ cytochemical staining with a post-azo-coupling method using a chromogenic substrate (Z-arg-arg-MNA) or by a novel assay placing the tissue section directly in a cuvette using the fluorogenic substrate Z-arg-arg-AMC. RESULTS Enzymatic activity, measured either in frozen sections in situ or in the cuvette assay, was positively correlated with joint destruction (r = 0.7) and inflammation (r = 0.8). Activity was not inhibited significantly by Pefabloc (a serine protease inhibitor), EDTA (a metalloprotease inhibitor), or pepstatin A (an aspartyl protease inhibitor) but was inhibited by E-64 and vinyl sulfone irreversible inhibitors of cysteine proteases. The effect of one of the vinyl sulfone cysteine protease inhibitors, Mu-Leu-HomoPhe-vinylsulfone, was tested in vivo by dietary administration at 2.2 mg/kg/day in the AIA model; this resulted in a significant decrease in inflammation and in the amount of cysteine protease activity measured in the joint tissue. CONCLUSION Cysteine protease activity levels increase in the diseased state and may be an important target for designing small molecule inhibitors to reduce the inflammation and tissue destruction associated with RA.
Fill‐in and infill errors in order memory

Many current models of memory are specified with enough detail to make predictions about patterns of errors in memory tasks. However, there are often not enough empirical data available to test these predictions. We report two experiments that examine the relative frequency of fill‐in and infill errors. In immediate serial recall tasks, subjects sometimes incorrectly recall item N too soon, placing it in position N−1. The error of interest is which item is recalled after this initial mistake. A fill‐in error is the tendency to recall item N−1 next, whereas an infill error is the tendency to recall item N+1 next. Both experiments reveal more fill‐in than infill errors, not only overall but at each possible error location throughout the list. The overall ratio is approximately 2:1. We conclude that none of the currently existing models adequately accounts for fill‐in and infill errors.
Genetic association of hypertension and vascular changes in stroke-prone spontaneously hypertensive rats.

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractile activity in response to norepinephrine, whereas those from normotensive Wistar-Kyoto rats (WKY) do not. To determine whether the norepinephrine-induced oscillations are related to high blood pressure or to separable genetic differences between strains, the response to norepinephrine was studied in adult SHRSP, WKY, and progeny of genetic crosses of SHRSP and WKY (F1, F2, F1 X SHRSP, F1 X WKY). Helical tail artery strips were mounted in a tissue bath for isometric force recording. Rats were classified as responders if oscillatory activity in the presence of 1.8 X 10(-7) M norepinephrine exceeded 250 mg/10 min (milligrams of force amplitude during a 10-minute interval). The blood pressures (mm Hg +/- SEM; tail cuff method) and percentage of rats exhibiting norepinephrine-induced oscillations were as follows: WKY: 109 +/- 3, 0%; F1: 129 +/- 4, 0%; F2: 150 +/- 4, 38%; F1 X WKY: 137 +/- 3, 9%; F1 X SHRSP: 188 +/- 7, 71%; SHRSP: 207 +/- 7, 100%. The distribution of the frequency of animals with oscillatory activity among the progenies was consistent with the hypothesis that a single gene locus determines the observed difference in oscillatory activity between the WKY and SHRSP strains. The allele from the SHRSP that determines the activity phenotype is recessive to the allele contributed by the normotensive WKY strain. In the segregating F2 progeny, the blood pressure of the responders was higher than that of the nonresponders (161 +/- 6 vs 144 +/- 4 mm Hg; p less than 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)
Legal system involvement and costs for persons in treatment for severe mental illness and substance use disorders.

OBJECTIVE Persons with co-occurring severe mental illness and substance use disorders were followed for three years to better understand how they are involved with the legal system and to identify factors associated with different kinds of involvement. METHODS Data came from a three-year study of 203 persons enrolled in specialized treatment for dual disorders. Cost and utilization data were collected from multiple data sources, including police, sheriffs and deputies, officers of the court, public defenders, prosecutors, private attorneys, local and county jails, state prisons, and paid legal guardians. RESULTS Over three years 169 participants (83 percent) had contact with the legal system, and 90 (44 percent) were arrested at least once. Participants were four times more likely to have encounters with the legal system that did not result in arrest than they were to be arrested. Costs associated with nonarrest encounters were significantly less than costs associated with arrests. Mean costs per person associated with an arrest were $2,295, and mean costs associated with a nonarrest encounter were $385. Combined three-year costs averaged $2,680 per person. Arrests and incarcerations declined over time. Continued substance use and unstable housing were associated with a greater likelihood of arrest. Poor treatment engagement was associated with multiple arrests. Men were more likely to be arrested, and women were more likely to be the victims of crime. CONCLUSIONS Effective treatment of substance use among persons with mental illness appears to reduce arrests and incarcerations but not the frequency of nonarrest encounters. Stable housing may also reduce the likelihood and number of arrests.
An αII Spectrin-Based Cytoskeleton Protects Large-Diameter Myelinated Axons from Degeneration

Axons must withstand mechanical forces, including tension, torsion, and compression. Spectrins and actin form a periodic cytoskeleton proposed to protect axons against these forces. However, because spectrins also participate in assembly of axon initial segments (AISs) and nodes of Ranvier, it is difficult to uncouple their roles in maintaining axon integrity from their functions at AIS and nodes. To overcome this problem and to determine the importance of spectrin cytoskeletons for axon integrity, we generated mice with αII spectrin-deficient peripheral sensory neurons. The axons of these neurons are very long and exposed to the mechanical forces associated with limb movement; most lack an AIS, and some are unmyelinated and have no nodes. We analyzed αII spectrin-deficient mice of both sexes and found that, in myelinated axons, αII spectrin forms a periodic cytoskeleton with βIV and βII spectrin at nodes of Ranvier and paranodes, respectively, but that loss of αII spectrin disrupts this organization. Avil-cre;Sptan1f/f mice have reduced numbers of nodes, disrupted paranodal junctions, and mislocalized Kv1 K+ channels. We show that the density of nodal βIV spectrin is constant among axons, but the density of nodal αII spectrin increases with axon diameter. Remarkably, Avil-cre;Sptan1f/f mice have intact nociception and small-diameter axons, but severe ataxia due to preferential degeneration of large-diameter myelinated axons. Our results suggest that nodal αII spectrin helps resist the mechanical forces experienced by large-diameter axons, and that αII spectrin-dependent cytoskeletons are also required for assembly of nodes of Ranvier. SIGNIFICANCE STATEMENT A periodic axonal cytoskeleton consisting of actin and spectrin has been proposed to help axons resist the mechanical forces to which they are exposed (e.g., compression, torsion, and stretch). However, until now, no vertebrate animal model has tested the requirement of the spectrin cytoskeleton in maintenance of axon integrity. We demonstrate the role of the periodic spectrin-dependent cytoskeleton in axons and show that loss of αII spectrin from PNS axons causes preferential degeneration of large-diameter myelinated axons. We show that nodal αII spectrin is found at greater densities in large-diameter myelinated axons, suggesting that nodes are particularly vulnerable domains requiring a specialized cytoskeleton to protect against axon degeneration.
LDL-C goal attainment with ezetimibe plus simvastatin coadministration vs atorvastatin or simvastatin monotherapy in patients at high risk of CHD.

AIMS To compare the proportion of patients at high risk for coronary heart disease (CHD) achieving the recommended low-density lipoprotein cholesterol (LDL-C) treatment goal of < 100 mg/dL and the optional LDL-C target of < 70 mg/dL with coadministration of ezetimibe and simvastatin (EZE/SIMVA) vs either atorvastatin or simvastatin monotherapy. PATIENTS Patients with established CHD or CHD risk equivalent according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with baseline LDL-C = 130 mg/dL and triglycerides (TG) < or = 350 mg/dL. METHODS A post hoc analysis from 2 separate studies assessed the percentage of high-risk patients achieving the LDL-C targets (< 100 and < 70 mg/dL) after 6 weeks on the usual recommended starting doses of the following treatments: EZE/SIMVA (10/20 mg) vs atorvastatin (10 mg) or simvastatin (20 mg). Depending on the study, EZE/SIMVA 10/10 or 10/40 mg was also compared with either atorvastatin 10 mg or simvastatin 20 mg. Percent change in other lipid parameters from baseline to study endpoint was also examined. RESULTS In both studies, the proportions of patients achieving an LDL-C of < 100 mg/dL were significantly (P < .001) greater for EZE/SIMVA 10/10, 10/20, or 10/40 mg vs either atorvastatin 10 mg or simvastatin 20 mg after 6 weeks. The percentage reaching the optional LDL-C treatment target of < 70 mg/dL was also significantly higher with EZE/SIMVA compared with either atorvastatin or simvastatin. Percent reduction in LDL-C was significantly (P < .001) larger with all doses of EZE/SIMVA (46% to 59%) compared with either atorvastatin 10 mg (37%) or simvastatin 20 mg (38%) monotherapy after 6 weeks. Changes in other lipid parameters consistently favored EZE/SIMVA vs statin monotherapy. All treatments were well tolerated in both studies. CONCLUSION Patients at high risk for CHD are more likely to attain LDL-C treatment targets with the usual recommended starting dose of EZE/SIMVA (10 or 20 mg) therapy than with that of atorvastatin (10 mg) or simvastatin (20 mg) monotherapy.
Gender-related needs and preferences in cancer care indicate the need for an individualized approach to cancer patients.

AIM Improving quality of care for cancer patients requires insight into their specific wishes, needs, and preferences concerning cancer care. The aim of this study was to explore the impact of gender on cancer patients' needs and preferences. PATIENTS AND METHODS Data were obtained from 386 questionnaires assessing cancer patients' preferences for health care. Multivariate regression analyses were performed with data obtained from medical oncology patients treated in seven Dutch hospitals, using the scales of the questionnaire as dependent variables. RESULTS Patients rated safety, expertise, performance, and attitude of physicians and nurses highest on their list of preferences. There were significant differences between male and female patients concerning preferences in health care in 15 of the 21 scales and in two of the eight single items. Without exception, women found the care aspects mentioned in these scales and items more important than men. Multivariate regression analysis showed that, of all the patient- and disease-related factors, gender was the most important independent predictor of patient preferences. CONCLUSION Gender impacts cancer patients' needs and preferences and should be taken into account for optimal cancer care. Cancer care might be tailored toward gender, for example, with regard to the means and extent of communication, manner and extent of support, counseling and rehabilitation, consultation length, and physician assignment. The results of this study may guide health care professionals and organizations to develop a gender-specific health care approach to further improve cancer patient-centered care.
ERα-XPO1 Cross Talk Controls Tamoxifen Sensitivity in Tumors by Altering ERK5 Cellular Localization

Most breast cancer deaths occur in women with recurrent, estrogen receptor (ER)-α(+), metastatic tumors. There is a critical need for therapeutic approaches that include novel, targetable mechanism-based strategies by which ERα (+) tumors can be resensitized to endocrine therapies. The objective of this study was to validate a group of nuclear transport genes as potential biomarkers to predict the risk of endocrine therapy failure and to evaluate the inhibition of XPO1, one of these genes as a novel means to enhance the effectiveness of endocrine therapies. Using advanced statistical methods, we found that expression levels of several of nuclear transport genes including XPO1 were associated with poor survival and predicted recurrence of tamoxifen-treated breast tumors in human breast cancer gene expression data sets. In mechanistic studies we showed that the expression of XPO1 determined the cellular localization of the key signaling proteins and the response to tamoxifen. We demonstrated that combined targeting of XPO1 and ERα in several tamoxifen-resistant cell lines and tumor xenografts with the XPO1 inhibitor, Selinexor, and tamoxifen restored tamoxifen sensitivity and prevented recurrence in vivo. The nuclear transport pathways have not previously been implicated in the development of endocrine resistance, and given the need for better strategies for selecting patients to receive endocrine modulatory reagents and improving therapy response of relapsed ERα(+) tumors, our findings show great promise for uncovering the role these pathways play in reducing cancer recurrences.
Comparison of reverse transcription-polymerase chain reaction, immunohistochemistry, and fluorescence in situ hybridization methodologies for detection of echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase fusion-positive non-small cell lung carcinoma: implications for optima

CONTEXT Echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase (EML4-ALK) gene fusions are detected in 3% to 13% of non-small cell lung carcinomas. Accurate testing for detection of EML4-ALK fusions is essential for appropriate therapy selection. OBJECTIVE To compare reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) methodologies for detection of EML4-ALK fusions. DESIGN Forty-six pulmonary adenocarcinomas were selected with enrichment for wild-type epidermal growth factor receptor (EGFR) status (wild type, n = 42; mutant, n = 4). Specimens were tested by IHC (Dako; clone ALK1), FISH (Abbott Molecular; LSI ALK break apart), and RT-PCR (variants 1 and 3a/b). RESULTS EML4-ALK variant 3a/b was detectable by RT-PCR, FISH, and IHC in 4% (2 of 46) of specimens. Complete agreement among FISH and IHC reviewers was obtained for variant 3a/b. No concordance existed among methodologies for the detection of EML4-ALK variant 1. The RT-PCR method detected variant 1 in 20% (9 of 46) of specimens. Agreement among FISH viewers was poor for variant 1 because only 11% (1/9) of specimens were scored as positive by all 3 viewers. The sensitivity of IHC for detection of variant 1 was also poor because only 1 of 9 samples (11%) was scored as positive. Overall, the frequency of EML4-ALK variants 1 and 3a/b was 24% (11 of 46) in adenocarcinomas enriched for wild-type EGFR status. One EML4-ALK variant 1 fusion was found to coexist with an EGFR exon 21 mutation. CONCLUSIONS The FISH interpretation demonstrated great variability among observers. The RT-PCR method was the most sensitive and least-subjective methodology for detection of EML4-ALK fusions.
Time‐dependent changes in caspase‐3 activity and heat shock protein 25 after spinal cord transection in adult rats

Chronic reductions in muscle activation and loading are associated with decreased heat shock protein 25 (Hsp25) expression and phosphorylation (pHsp25) which, in turn, may contribute to elevated caspase‐3‐mediated muscle protein breakdown. Thus, the purpose of the present study was to determine whether there are any changes in Hsp25, pHsp25 and caspase‐3 activity among rat muscles having different fibre type compositions and functions [soleus, adductor longus (AL), plantaris and tibialis anterior (TA)] at 0 (control), 1, 8 or 28 days after a complete spinal cord transection (ST). The Hsp25 levels were unaffected on days 1 and 8 in all muscles, except for a significant reduction on day 8 in plantaris. The Hsp25 levels were lower than control values in all muscles except TA on day 28. The pHsp25 levels were lower than control values after 8 and 28 days in plantaris and AL and after 28 days in soleus, but higher than control in TA after 8 and 28 days. Caspase‐3 activity was higher in ST than control rats on day 8 in all muscles except TA. Caspase‐3 activity was negatively correlated with muscle mass for all muscles. In plantaris, Hsp25 and pHsp25 were negatively correlated with caspase‐3 activity and Hsp25 was correlated with muscle mass. These relationships were not observed in other muscles. Thus, the effects of ST on Hsp25 and caspase‐3 are muscle specific and time dependent, factors that should be considered in developing any intervention to maintain muscle mass after a spinal cord injury.
Modelling whale-vessel encounters: the role of speed in mitigating collisions with humpback whales (Megaptera novaeangliae)

Increasing whale populations and vessel traffic worldwide has led to an increase in reported whale-vessel collisions. This paper reports on factors that affect the rate of whale-vessel collisions in the four-island region of Maui, Hawai’i. More specifically, it aims at quantifying the probability of a whale-vessel collision with varying vessel speeds using encounter distances as a proxy. A change point model was used to identify a speed threshold of 12.5kts (6.4m/s), which showed a significant change in the relationship between speed and mean sighting distance. A 3.4-fold decrease in close encounters with humpback whales was observed when vessels travelled at speeds of 12.5kts (6.4m/s) or less. Furthermore, results indicate that lone adult whales and calves are the most likely to be involved in a collision. A speed limit of 12.5kts (6.4m/s) is warranted in areas and/or during seasons where a high density of whales occurs. This limit aligns with a reduction in lethal vessel strikes with speed from previous studies which found a significant increase in the likelihood of mortality when vessel speed exceeds 12kts.
Hyperuricaemia in patients with type 2 diabetes in a tertiary healthcare centre in sub-Saharan Africa: prevalence and determinants

Hyperuricaemia in type 2 diabetes mellitus (T2DM) has been less well investigated in sub-Saharan Africans. Our study of 438 patients found that alcohol intake, body mass index ≥25 kg/m2, hydrochlorothiazide use, statin use, diabetic retinopathy and glomerular filtration rate <60 mL/min/1.73m2 were independently positively associated with hyperuricaemia; whereas smoking reduced this risk. Hyperuricaemia is strongly associated with some modifiable factors, diabetic complications and certain drugs. Our results suggest that further studies should evaluate the potential cost–benefit of screening for hyperuricaemia in type 2 diabetes.
DP-GAN: Dual Pathway Generative Adversarial Network for Face Recognition in Degraded Scenarios

Face Recognition (FR) using Convolutional Neural Network (CNN) based models have achieved considerable success in constrained environments. They however fail to perform well in unconstrained scenarios, especially when the images are captured using surveillance cameras. These probe samples suffer from degradations such as noise, poor illumination, low resolution, blur as well as aliasing, when compared to the rich training (gallery) set, comprising mostly of mugshot images captured in laboratory settings. These images in the training (gallery) set are crisp and have high contrast, compared to the probe samples. To cope with this scenario, we propose a novel dual-pathway generative adversarial network (DP-GAN) which maps low resolution images captured using surveillance camera into their corresponding high resolution images, which are gallery-like, using a novel combination of multi-scale reconstruction and Jensen-Shannon divergence based loss. These images thus obtained are then used to train a deep domain adaptation (deep-DA) network to perform the task of FR. The proposed network achieves superior results (>90%) on four benchmark surveillance face datasets, evident from the rank-1 recognition rates when compared with recent state-of-the-art CNN-based techniques.
Physical activity, physical fitness, and coronary heart disease risk factors in youth: the Québec Family Study.

OBJECTIVE The relationships between physical activity, fitness, and CHD risk factors were investigated in 342 males and 268 females 9-18 years of age. METHODS Daily energy expenditure, moderate to vigorous physical activity, inactivity, and television viewing time were estimated. Indicators of physical fitness included submaximal work capacity, quadriceps muscle strength, sit-ups, and the sum of six skinfolds. Risk factors included mean arterial blood pressure and fasting blood levels of triglycerides, LDL-cholesterol, HDL-cholesterol, and glucose. RESULTS Canonical correlations between activity and risk factor profiles range from 0.22 to 0.45, while those between fitness and risk factor profiles range from 0.34 to 0.55, indicating that 5 to 20% and 11 to 30% of the variance in the risk profile is explained by activity and fitness, respectively. CONCLUSION The results suggest that both physical fitness and level of habitual physical activity are strongly associated with CHD risk factors in this sample of youth.
Outcome assessment for epilepsy surgery: The impact of measuring health‐related quality of life

Epilepsy surgery is an increasingly common treatment for intractable epilepsy; yet there is no clear consensus among experts on how to report epilepsy surgery outcome. Most published outcome reporting systems focus on seizure frequency and type but differ in how they define clinically distinct outcome categories. We used a reliable and valid measure of self‐reported health‐related quality of life (HRQOL), the Epilepsy Surgery Inventory (ESI)‐55, as an external standard by which to evaluate seven previously published, seizure‐based outcome classification systems. The ESI‐55 was administered to 133 adults who had previously undergone surgery for intractable epilepsy, and results were linked to data on their seizure occurrence before and after surgery (over the year prior to their HRQOL reports). These 133 patients were classified according to each seizure‐based outcome system, and variation in HRQOL across outcome groups was evaluated using analysis of variance. Results reveal noteworthy variation in the extent to which different systems reflect patients' HRQOL at follow‐up. We modified existing systems to derive a seizure‐based surgery outcome system that most closely reflects HRQOL when applied over the latest 1‐year postoperative interval.