Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of the timing of antiretroviral therapy on the potential for normalization of immune status in human immunodeficiency virus 1-infected individuals.

IMPORTANCE In individuals with human immunodeficiency virus 1 (HIV-1) infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized. OBJECTIVE To investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4+ T-cell counts, AIDS risk, and immune function. DESIGN, SETTING, AND PARTICIPANTS Participants in the observational US Military HIV Natural History Study with documented estimated dates of seroconversion (EDS) who achieved virologic suppression with ART were evaluated. Markers indicative of immune activation, dysfunction, and responsiveness were determined. Responses to hepatitis B virus (HBV) vaccine, an indicator of in vivo immune function, were also assessed. The timing of ART was indexed to the EDS and/or entry into the cohort. The CD4+ counts in HIV-1-uninfected populations were surveyed. MAIN OUTCOMES AND MEASURES Normalization of CD4+ counts to 900 cells/μL or higher, AIDS development, HBV vaccine response, as well as T-cell activation, dysfunction, and responsiveness. RESULTS The median CD4+ count in HIV-1-uninfected populations was approximately 900 cells/μL. Among 1119 HIV-1-infected participants, CD4+ normalization was achieved in 38.4% vs 28.3% of those initiating ART within 12 months vs after 12 months from the EDS (P = .001). Incrementally higher CD4+ recovery (<500, 500-899, and ≥900 cells/μL) was associated with stepwise decreases in AIDS risk and reversion of markers of immune activation, dysfunction, and responsiveness to levels approximating those found in HIV-1-uninfected persons. Participants with CD4+ counts of 500 cells/μL or higher at study entry (adjusted odds ratio [aOR], 2.00; 95% CI, 1.51-2.64; P < .001) or ART initiation (aOR, 4.08; 95% CI, 3.14-5.30; P < .001) had significantly increased CD4+ normalization rates compared with other participants. However, even among individuals with a CD4+ count of 500 cells/μL or higher at both study entry and before ART, the odds of CD4+ normalization were 80% lower in those initiating ART after 12 months from the EDS and study entry (aOR, 0.20; 95% CI, 0.07-0.53; P = 001). Initiation of ART within 12 months of EDS vs later was associated with a significantly lower risk of AIDS (7.8% vs 15.3%; P = .002), reduced T-cell activation (percent CD4+HLA-DR+ effector memory T cells, 12.0% vs 15.6%; P = .03), and increased responsiveness to HBV vaccine (67.9% vs 50.9%; P = .07). CONCLUSIONS AND RELEVANCE Deferral of ART beyond 12 months of the EDS diminishes the likelihood of restoring immunologic health in HIV-1-infected individuals.
A Mouse Model of Embolic Focal Cerebral Ischemia

We developed a mouse model of embolic focal cerebral ischemia, in which a fibrin-rich clot was placed at the origin of the middle cerebral artery (MCA) in C57BL/6J mice (n = 31) and B6C3 mice (n = 10). An additional three non-embolized C57BL/6J mice were used as a control. Embolus induction, cerebral vascular perfusion deficit, and consequent ischemic cell damage were confirmed by histopathology, immunohistochemistry, laser confocal microscopy, and regional cerebral blood flow (rCBF) measurements. Reduction in rCBF and cerebral infarct were not detected in the control animals. An embolus was found in all C57BL/6J and B6C3 mice at 24 hours after injection of a clot. Regional CBF in the ipsilateral parietal cortex decreased to 23% (P < 0.05) and 17% (P < 0.05) of preembolization levels immediately and persisted for at least 1 hour in C57BL/6J mice (n = 6) and in B6C3 mice (n = 3), respectively. A significant decrease of rCBF was accompanied by a corresponding reduction of plasma perfusion in the ipsilateral MCA territory. Neurons exhibited marked reduction in microtubule-associated protein-2 immunostaining coincident with the area of perfusion deficit. The percent infarct volume was 30.3% ± 13.4% for C57BL/6J mice (n = 17), and 38.3% ± 15.3% for B6C3 mice (n = 7) at 24 hours after embolization. This model of embolic ischemia is relevant to thromboembolic stroke in humans and may be useful to investigate embolic cerebral ischemia in the genetically altered mouse and for evaluation of antiembolic therapies.
Impact of Grazing Intensity during Drought in an Arizona Grassland

Abstract: The ecological benefits of changing cattle grazing practices in the western United States remain controversial, due in part to a lack of experimentation. In 1997 we initiated an experimental study of two rangeland alternatives, cattle removal and high‐impact grazing, and compared grassland community responses with those with more conventional, moderate grazing practices. The study was conducted in a high‐elevation, semiarid grassland near Flagstaff, Arizona (U.S.A.). We conducted annual plant surveys of modified Whittaker plots for 8 years and examined plant composition shifts among treatments and years. High‐impact grazing had strong directional effects that led to a decline in perennial forb cover and an increase in annual plants, particularly the exotic cheatgrass (Bromus tectorum L.). A twofold increase in plant cover by exotic species followed a severe drought in the sixth year of the study, and this increase was greatest in the high‐impact grazing plots, where native cover declined by one‐half. Cattle removal resulted in little increase in native plant cover and reduced plant species richness relative to the moderate grazing control. Our results suggest that some intermediate level of cattle grazing may maintain greater levels of native plant diversity than the alternatives of cattle removal or high‐density, short‐duration grazing practices. Furthermore, episodic drought interacts with cattle grazing, leading to infrequent, but biologically important shifts in plant communities. Our results demonstrate the importance of climatic variation in determining ecological effects of grazing practices, and we recommend improving conservation efforts in arid rangelands by developing management plans that anticipate this variation.
Accounting in the late medieval town: the account books of the stewards of Southampton in the fifteenth century

The fifteenth-century account books of the Southampton town officer known as the steward are the main source used here for a study of accounting in the late medieval town. The article considers internal and external influences on Southampton's early change to paper account books, improved presentation of accounting information and use of English in the stewards' books. It explores the links between writing materials, format and language in the preparation of town accounts at Southampton and other towns. The article concludes by suggesting that the classified account introduced in the steward's book of 1441-2 is evidence of a wider function for charge/discharge accounting than is normally attributed to it.
Role of metronidazole resistance in therapy of Helicobacter pylori infections

Susceptibility to metronidazole was determined by disk diffusion tests for 559 strains of Helicobacter pylori isolated from patients. The overall metronidazole resistance was 26%. In males metronidazole-resistant strains made 18% of all H. pylori strains, and in females the corresponding figure was 40% (P less than 0.001). MICs of metronidazole were determined for H. pylori strains from 86 patients undertaking triple therapy, i.e., treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. Of the nonresponders who remained culture positive despite the therapy, 69% had strains with metronidazole MICs of greater than or equal to 32 micrograms/ml before the therapy, and all nonresponders had metronidazole-resistant strains after the therapy. Metronidazole resistance was, however, also found in 27% of responders before therapy. To find whether the MICs of metronidazole for H. pylori strains remained constant for longer periods, consecutive isolates sampled several years apart from the same patients were tested in parallel and no changes in the MICs were found. H. pylori was successfully eradicated by the triple therapy from 91% of patients with metronidazole-susceptible pretreatment strains and from 63% of patients with metronidazole-resistant strains before the therapy (P less than 0.01). Although resistance to metronidazole has a significant role in treatment failures in H. pylori infections, high eradication rates can be achieved with the use of the present triple therapy even in populations with a high overall metronidazole resistance rate.
Assessing the Impact of Body Size in Childhood and Adolescence on Blood Pressure: An Application of Partial Least Squares Regression

Background: Recent studies have found that postnatal catch-up growth might have a stronger impact than birth size on health in later life. Because growth is a continuing process, the challenge is to tease out the impact of body size at different critical phases. Ordinary least squares regression cannot differentiate the effects of birth size, growth, and current body size simultaneously, because growth is generally defined as the difference between birth size and current size, giving rise to perfect collinearity. Methods: This paper aims to describe and justify the use of a novel approach, partial least squares, to estimate life course effects of body size z-scores on later blood pressure, using longitudinal data from a cohort of 960 Filipino boys. Body weight z-scores and changes in z-score weight were measured from birth to age 19 years, and systolic and diastolic blood pressures (BPs) were measured at age 19. Results: In general, birth size had a very modest association with systolic BP. The early changes in z-scores between birth and the age of 2 years were positively associated with the outcome. Growth after age 8 had a larger effect than early growth, but the confidence intervals are generally large. For diastolic BP, the association was similar for early and later growth. Current body size had the strongest relationships with both outcomes. Conclusion: By creating weighted composites of perfectly collinear variables as components, partial least squares estimates the life course effects of body size on later health according to the correlations between body size and health outcomes.
Langerhans cells in squamous cell carcinoma vs. pseudoepitheliomatous hyperplasia of the skin

Background: In clinical and histopathological practice, it is sometimes difficult to distinguish pseudoepitheliomatous hyperplasia (PEH) from squamous cell carcinoma (SCC) of the skin. Several studies have shown a low density of Langerhans cells in SCC of the skin, and recent research on cervical SCCs has suggested that the decreased density of dendritic cells is secondary to low E‐cadherin expression. SCCs of the head and neck similarly have decreased E‐cadherin expression, but E‐cadherin expression is preserved in PEH. We hypothesized that PEH of the skin would have an increased number of Langerhans cells compared with SCC.
Anti-apoptotic Protein BCL2 Down-regulates DNA End Joining in Cancer Cells*

Cancer cells are often associated with secondary chromosomal rearrangements, such as deletions, inversions, and translocations, which could be the consequence of unrepaired/misrepaired DNA double strand breaks (DSBs). Nonhomologous DNA end joining is one of the most common pathways to repair DSBs in higher eukaryotes. By using oligomeric DNA substrates mimicking various endogenous DSBs in a cell-free system, we studied end joining (EJ) in different cancer cell lines. We found that the efficiency of EJ varies among cancer cells; however, there was no remarkable difference in the mechanism and expression of EJ proteins. Interestingly, cancer cells with lower levels of EJ possessed elevated expression of BCL2 and vice versa. Removal of BCL2 by immunoprecipitation or protein fractionation led to elevated EJ. More importantly, we show that overexpression of BCL2 or the addition of purified BCL2 led to the down-regulation of EJ. Further, we found that BCL2 interacts with KU proteins both in vitro and in vivo. Hence, our results suggest that EJ in cancer cells could be negatively regulated by the anti-apoptotic protein, BCL2, and this may contribute toward increased chromosomal abnormalities in cancer.
The WHO histological classification of tumors of the gallbladder and extrahepatic bile ducts. A commentary on the second edition

The second edition of the WHO Histological Classification of Tumors of the Gallbladder and Extrahepatic Bile Ducts is more comprehensive and detailed than the previous one. Advances in our understanding of dysplasia, carcinoma in situ, various lines of differentiation among the carcinomas, and the recognition of a variety of tumor‐like lesions have resulted in more than three times as many entities in the current classification as in the previous one. The new edition should facilitate pathologic, epidemiologic, and therapeutic comparisons. Cancer 1992; 70:410–414.
Cardiovascular , Pulmonary and Renal Pathology Diabetic Albuminuria Is Due to a Small Fraction of Nephrons Distinguished by Albumin-Stained Tubules and Glomerular Adhesions

OVE26 diabetic mice develop severe albuminuria. Immunohistochemical analysis revealed a pattern of intense albumin staining in a small subset of OVE26 tubules. Immunostaining was strikingly heterogeneous; some tubules stained intensely for albumin, but most tubules had weak or no staining. Serial sectioning showed that staining patterns were distinctive for each nephron. Electron microscopy revealed that albumin accumulated in villi and at the base of the brush border. Tubule cell injury, as shown by loss of villi , tubule dilation, and cellular protrusions into the tubule lumen, was unambiguously associated with albumin staining. Examination of albumin staining of proteinuric human kidneys also showed a heterogeneous pattern of staining. Analysis of OVE26 serial sections indicated that all glomeruli connected to albumin-positive tubules were identified by albuminstained lesions in the tuft that adhered to Bowman’s capsule, implicating this as a critical feature of heavy albumin leakage. These results indicate that albumin accumulation provides a marker of damaged nephrons, and confirm that albumin leakage produces significant tubular damage. This study shows that that formation of sclerotic glomerular adhesions is a critical step leading to severe albuminuria. (Am J Pathol 2009, 175:500–509; DOI: 10.2353/ajpath.2009.080939)
Subthreshold mood symptoms in patients with fibromyalgia and rheumatoid arthritis.

OBJECTIVES Although several findings have highlighted the prevalence of Axis I psychiatric disorders in fibromyalgia (FM) and rheumatoid arthritis (RA), very little information is available on the prevalence of subthreshold mood symptoms in these conditions. Therefore, we aimed at comparing the prevalence of subthreshold mood symptoms in rheumatic patients suffering from FM and RA. The hypothesis is that subthreshold mood symptoms are more represented in FM, given the evidence of higher rates of Axis I psychopathology in FM than in RA. METHODS Sixty patients suffering from FM and 50 from RA, assessed according to the American College of Rheumatology (ACR) criteria, selected in a Rheumatology Department, were included in the study. The subthreshold affective symptoms were assessed by means of the Mood Spectrum-Self Report (MOODS-SR). RESULTS The results showed that FM patients presented significantly higher scores than RA patients in 'mood depressive', 'cognition depressive' domains and in total depressive component. CONCLUSIONS The present study demonstrates that subthreshold depressive symptoms are more represented in FM than in RA patients. This fact could play a role in the worse quality of life and in the major perception of pain which characterises FM.
Socio-demographic, lifestyle and psychological predictors of benzodiazepine and z-hypnotic use patterns

Abstract Aims: Risk and demographic factors for benzodiazepine and z-hypnotic use are incompletely understood. The aim of the paper was therefore to investigate socio-demographic, lifestyle and psychological factors predicting onset and differential pattern of prescribed benzodiazepine and z-hypnotic use in a Norwegian population sample. Methods: This retrospective cohort study obtained socio-demographic, psychological and lifestyle variables from the Nord-Trøndelag Health Study. Information about benzodiazepine prescriptions from the Norwegian prescription database were linked to epidemiological questionnaire data. Benzodiazepine use was classified into single-period, intermittent and chronic use, and high dose use was defined as being prescribed a yearly average above 180 daily defined doses. Results: Older age, sleep difficulties and smoking were positively associated with all patterns of benzodiazepine use. Male gender was related to a reduced risk of all patterns of use, whereas educational achievement was negatively associated with single-period use. Alcohol consumption, anxiety and tension were positively related to intermittent and chronic use, while exercise was negatively related to chronic use. Smoking, sleep difficulties and old age were positively associated with prescriptions of high benzodiazepine doses, while exercise was associated with lower doses. Conclusions: Patterns of prescribed benzodiazepine use are linked to demographic, lifestyle and clinical variables. Non-pharmacological treatment for sleep difficulties and smoking cessation may reduce the risk of chronic benzodiazepine use.
Using Backup Generators for Meeting Peak Electricity Demand: A Sensitivity Analysis on Emission Controls, Location, and Health Endpoints

Abstract Generators installed for backup power during blackouts could help satisfy peak electricity demand; however, many are diesel generators with nonnegligible air emissions that may damage air quality and human health. The full (private and social) cost of using diesel generators with and without emission control retrofits for fine particulate matter (PM2.5) and nitrogen oxides (NOx) were compared with a new natural gas turbine peaking plant. Lower private costs were found for the backup generators because the capital costs are mostly ascribed to reliability. To estimate the social costs from air quality, the changes in ambient concentrations of ozone (O3) and PM2.5 were modeled using the Particulate Matter Comprehensive Air Quality Model with extensions (PMCAMx) chemical transport model. These air quality changes were translated to their equivalent human health effects using concentration-response functions and then into dollars using estimates of “willingness-to-pay” to avoid ill health. As a case study, 1000 MW of backup generation operating for 12 hr/day for 6 days in each of four eastern U.S. cities (Atlanta, Chicago, Dallas, and New York) was modeled. In all cities, modeled PM2.5 concentrations increased (up to 5 µg/m3) due mainly to primary emissions. Smaller increases and decreases were observed for secondary PM2.5 with more variation between cities. Increases in NOx emissions resulted in significant nitrate formation (up to 1 µg/m3) in Atlanta and Chicago. The NOx emissions also caused O3 decreases in the urban centers and increases in the surrounding areas. For PM2.5, a social cost of approximately $2/kWh was calculated for uncontrolled diesel generators in highly populated cities but was under 10 ¢/kWh with PM2.5 and NOx controls. On a full cost basis, it was found that properly controlled diesel generators are cost-effective for meeting peak electricity demand. The authors recommend NOx and PM2.5 controls.
Preservation of Reasoning in Primary Progressive Aphasia: Further Differentiation from Alzheimer's Disease and the Behavioral Presentation of Frontotemporal Dementia

Primary Progressive Aphasia (PPA) is a clinical dementia syndrome characterized by the gradual dissolution of language without impairment of other cognitive domains for at least the first 2 years of illness (M.-M. Mesulam, 1982, 2001). It is difficult to demonstrate the integrity of nonlanguage domains in PPA because most neuropsychological tests of memory, reasoning, and attention require language competence for their performance. In the present study, reasoning and cognitive flexibility were tested nonverbally in patients with PPA using a modified ten-item version of the Visual Verbal Test (Feldman & Drasgow, 1959). This test measures the ability to detect similarities among objects and to sort a single set of objects according to two different principles. The performance of PPA patients (n = 20) was compared with that of patients with dementia of the Alzheimer type (AD) (n = 20), patients with the comportmental/executive dysfunction variant of frontotemporal dementia (FTD) (n = 16), and cognitively intact controls (n = 20). Patients with PPA and controls performed similarly, detecting commonalities among objects and shifting from one sorting principle to another. In contrast, both AD and FTD subjects were significantly impaired on both measures. These results provide evidence of preserved reasoning in PPA, further differentiating this syndrome from other behaviorally focal dementia syndromes.
Accurate and Efficient Evaluation of Spatial Electromagnetic Responses of Large Scale Targets

An error controllable algorithm is proposed to efficiently evaluate two-dimensional (2-D) monostatic radar cross section (RCS) from electrically large and complex targets. The algorithm employs interpolative decomposition (ID) to conduct low-rank decomposition on the excitation matrix consisting of multiple right-hand-sides (RHS's) to figure out the so-called skeleton incidents. After the solutions corresponding to skeletons are obtained, the complete angular responses can be recovered efficiently. The proposed algorithm is error controllable because the accuracy/resolution of the excitation matrix and ID can both be manipulated. The algorithm is efficient in terms of CPU time due to the high efficiency of ID. For large scale problems, the number of unknowns and that of incidents become large, which, in turn, would lead to a huge excitation matrix. A multiinterval variation is proposed to overcome the possible bottle-neck on memory usage. The proposed method is user-friendly because all the tunable parameters are problem independent. Numerical experiments on electrically large and complex targets have been performed to show the performance of the proposed algorithm.