Miracle-dz/UniFAR-FTUs huggingface dataset:
Limited Neutralizing Antibody Specificities Drive Neutralization Escape in Early HIV-1 Subtype C Infection

We previously showed that HIV-1 subtype C viruses elicit potent but highly type-specific neutralizing antibodies (nAb) within the first year of infection. In order to determine the specificity and evolution of these autologous nAbs, we examined neutralization escape in four individuals whose responses against the earliest envelope differed in magnitude and potency. Neutralization escape occurred in all participants, with later viruses showing decreased sensitivity to contemporaneous sera, although they retained sensitivity to new nAb responses. Early nAb responses were very restricted, occurring sequentially and targeting only two regions of the envelope. In V1V2, limited amino acid changes often involving indels or glycans, mediated partial or complete escape, with nAbs targeting the V1V2 region directly in 2 cases. The alpha-2 helix of C3 was also a nAb target, with neutralization escape associated with changes to positively charged residues. In one individual, relatively high titers of anti-C3 nAbs were required to drive genetic escape, taking up to 7 weeks for the resistant variant to predominate. Thereafter titers waned but were still measurable. Development of this single anti-C3 nAb specificity was associated with a 7-fold drop in HIV-1 viral load and a 4-fold rebound as the escape mutation emerged. Overall, our data suggest the development of a very limited number of neutralizing antibody specificities during the early stages of HIV-1 subtype C infection, with temporal fluctuations in specificities as escape occurs. While the mechanism of neutralization escape appears to vary between individuals, the involvement of limited regions suggests there might be common vulnerabilities in the HIV-1 subtype C transmitted envelope.
Deaths by tuberculosis in a priority city for disease control in the Brazilian Northeast: sociodemographic-operational characteristics and vulnerable territories.

Introduction: Incorporating spatial approaches into epidemiological research is a challenge in public health research. The goal in this study was to analyze the spatial distribution of cases of deaths by tuberculosis in Imperatriz – MA (Brazil) and to characterize these events according to sociodemographic and operational characteristics. Methods: In this ecological study, all deaths from tuberculosis as the primary cause registered in the Mortality Information System from 2005 to 2014 were considered. The research variables were subject to descriptive analysis, point density analysis (Kernel Intensity Estimation) and area analysis. Results: Fifty cases of deaths by TB were identified, particularly the pulmonary clinical form. Male patients were predominant, with a median age of 59 years, mulatto race/color, single, who had finished secondary education. Most deaths happened at the hospital, with medical care before death and without autopsy. Most events happened at the hospital, with medical care delivery by an assistant physician and without autopsy. The point density revealed heterogeneity in the spatial distribution of the deaths, with rates of up to 2.33 deaths/km2. The area analysis by census sector presented age standardized mortality rates of 0.00 to 4.00 deaths/100,000 inhabitants-year. Conclusion: The results contributed to the knowledge on the spatial distribution of cases of deaths by Tuberculosis and their characteristics in the research scenario. The importance of space is highlighted as a methodological alternative to support the planning, monitoring and assessment of health actions, targeting interventions to the control of the disease in vulnerable territories. Keywords: Tuberculosis; Health Information Systems; Mortality; Spatial analysis.
Influence of Irradiation on Excess Currents in SiC pn Structures

Excess currents of the different nature in 6H-SiC pn structures of the different origin and parameters were investigated. The effect of the suppression of the forward and reverse excess currents were observed after 0.9 MeV electron (dose 5x1016 ÷ 1.6x1017 cm-2) and 8 MeV proton (dose 5x1015 cm-2) irradiation for structures with shunts which is probably due to the presence of relatively small inhomogeneities. The shunts in another group of pn structures probably are more high capability and they are more stable against degradation during irradiation.
Human T-cell lymphotropic virus type I and neurological diseases

Human T-cell lymphotropic virus type I (HTLV-I) infection is associated with a variety of human diseases. In particular, there are two major diseases caused by HTLV-I infection. One is an aggressive neoplastic disease called adult T-cell leukemia (ATL), and another is a chronic progressive inflammatory neurological disease called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is still unknown why one virus causes these different diseases. With regard to HAM/TSP, virus-host immunological interactions are an considered to be important cause of this disease. Coexisting high HTLV-I proviral load and HTLV-I-specific T cells (CD4+ T cells and CD8+ T cells) is an important feature of HAM/TSP. Histopathological studies indicate the existence of an inflammatory reaction and HTLV-I-infected cells in the affected lesions of HAM/TSP. Therefore, the immune response to HTLV-I probably contributes to the inflammatory process of the central nervous system lesions in HAM/TSP patients.
Minimum clinically important difference in medical studies

In clinical trials, minimum clinically important difference (MCID) has attracted increasing interest as an important supportive clinical and statistical inference tool. Many estimation methods have been developed based on various intuitions, while little theoretical justification has been established. This article proposes a new estimation framework of the MCID using both diagnostic measurements and patient‐reported outcomes (PROs). The framework first formulates the population‐based MCID as a large margin classification problem, and then extends to the personalized MCID to allow individualized thresholding value for patients whose clinical profiles may affect their PRO responses. More importantly, the proposed estimation framework is showed to be asymptotically consistent, and a finite‐sample upper bound is established for its prediction accuracy compared against the ideal MCID. The advantage of our proposed method is also demonstrated in a variety of simulated experiments as well as two phase‐3 clinical trials.
Production of freeze‐dried yeast culture for the brewing of traditional sorghum beer, tchapalo

Abstract Freeze‐drying is a well‐known dehydration method widely used to preserve microorganisms. In order to produce freeze‐dried yeast starter culture for the brewing purpose of African sorghum beer, we tested protective agents (sucrose, glucose, glycerol) in combination with support materials (millet, maize, sorghum, and cassava flours) at 1:1 ratio (v/v). The yeast strains Saccharomyces cerevisiae F 12–7 and Candida tropicalis C 0–7 previously isolated from sorghum beer were used in a mixed culture at a ratio of 2:1 (C. tropicalis/S. cerevisiae). After the freeze‐drying, the residual water contents were between 0.78 –2.27%, 0.55 –4.09%, and 0.40–2.61%, respectively, with sucrose, glucose and glycerol. The dried yeasts viabilities were between 4.0% and 10.6%. Among the protective agents used, sucrose was found to be the best protectant giving cell viabilities of 8.4–10.6%. Considering the support materials, millet flour was the best support after drying. When the freeze‐dried yeast powders were stored at 4°C and room temperature (25–28°C) for up to 3 months, the survival rates were the highest with cassava flour as the support material.
Maternal obesity and risk for birth defects.

OBJECTIVE Several studies have shown an increased risk for neural tube defects associated with prepregnancy maternal obesity. Because few recent studies have examined the relation between maternal prepregnancy obesity and overweight and other birth defects, we explored the relation for several birth defects and compared our findings with those of previous studies. METHODS We conducted a population-based case-control study of several selected major birth defects using data from the Atlanta Birth Defects Risk Factor Surveillance Study. Mothers who delivered an infant with and without selected birth defects in a 5-county metropolitan Atlanta area between January 1993 and August 1997 were interviewed. Maternal body mass index (BMI) was calculated from self-reported maternal prepregnancy weight and height. Women with known preexisting diabetes were excluded. The risks for obese women (BMI > or =30) and overweight women (BMI 25.0-29.9) were compared with those for average-weight women (BMI 18.5-24.9). RESULTS Obese women were more likely than average-weight women to have an infant with spina bifida (unadjusted odds ratio [OR]: 3.5; 95% confidence interval [CI]: 1.2-10.3), omphalocele (OR: 3.3; 95% CI: 1.0-10.3), heart defects (OR: 2.0; 95% CI: 1.2-3.4), and multiple anomalies (OR: 2.0; 95% CI: 1.0-3.8). Overweight women were more likely than average-weight women to have infants with heart defects (OR: 2.0; 95% CI: 1.2-3.1) and multiple anomalies (OR: 1.9; 95% CI: 1.1-3.4). CONCLUSIONS Our study confirmed the previously established association between spina bifida and prepregnancy maternal obesity and found an association for omphalocele, heart defects, and multiple anomalies among infants of obese women. We also found an association between heart defects and multiple anomalies and being overweight before pregnancy. A higher risk for some birth defects is yet another adverse pregnancy outcome associated with maternal obesity. Obesity prevention efforts are needed to increase the number of women who are of healthy weight before pregnancy.
The Safety of Quinolones in Pregnancy

Quinolones and fluoroquinolones are highly efficient antibiotics. However, concerns regarding possible harmful effects have limited their use during pregnancy. Nevertheless, accumulating clinical data suggest that they may be safe during pregnancy. This review aimed to explore the mechanisms of action of the quinolones and fluoroquinolones, which set the stage for concerns regarding possible teratogenic and mutagenic effects; to clarify the clinical dilemmas that brought forth the necessity in reevaluating the use of those medications during pregnancy; and to review the accumulated data regarding their safety during pregnancy in animal models and humans. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to assess the mechanisms of action that had led to concerns regarding the use of fluoroquinolones during pregnancy, appraise the basic knowledge gained from animal studies about the effects of fluoroquinolones during pregnancy, and analyze the human data on the actual effect of variable fluoroquinolones in pregnancy.
Generation of microcellular polyurethane with supercritical carbon dioxide

We examined the formation of microcellular foam in a thermoplastic polyurethane elastomer (TPU) with supercritical carbon dioxide. Measurements of the permeability and impregnation with carbon dioxide suggested that the impregnation of TPU with carbon dioxide was affected by the soft-segment chain length and soft-segment concentration in TPU and that carbon dioxide was mainly present in the soft-segment area. Thus, it seemed likely that the nucleation and growth of the nuclei in the microcells occurred in the soft-segment area. In addition, scanning electron microscopy of the microcells indicated that the higher the saturation pressure was, the smaller the mean cell diameter was; that is, the higher the cell number density was, the lower the foaming temperature was, the smaller the mean cell diameter was, and the lower the saturation pressure was, the more conspicuous this phenomenon was. These results showed that the saturation pressure and foaming temperature affected the cell structure. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Understanding Teenage Fertility, Cohabitation, and Marriage: The Case of Peru

In this study, we used data from the Young Lives study, which investigates teenage childbearing, marriage, and cohabitation by tracking a cohort of individuals from the ages of 8 to 19 years. While the present analysis does not intend to establish causality, the longitudinal nature of the data allows us to identify the combination of early circumstances and life changes that induce a higher likelihood of these events. The analysis addresses bias due both to reverse causality and to community characteristics that are usually unobserved and fixed over time, a strategy that is quite unique in studies of developing countries. About 1 out of 5 females (and 1 out of 20 males) in our sample had at least one child by the age of 19, and 80 percent of them were married or cohabiting. Early marriage/cohabitation is indeed intrinsically related to early pregnancy and largely predicted by the same factors. For females specifically, girls from poor households with an absent parent for a prolonged period have a higher risk of early childbearing. Similarly, girls whose self-efficacy and educational aspirations decrease over time are more at risk of becoming a mother during adolescence. Conversely, school attendance and better school performance predict a lower risk of early pregnancy; our analysis suggests that this is largely because it postpones the first sexual relationship.
A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging

Heterochromatin in aging stem cells Analysis of human aging syndromes, such as Werner syndrome (WS), may lead to greater understanding of both premature and normal aging. Zhang et al. generated isogenic WS-specific human embryonic stem cell lines (see the Perspective by Brunauer and Kennedy). WS-mesenchymal stem cells displayed features characteristic of premature aging, including heterochromatin disorganization. WRN protein thus functions in the maintenance of heterochromatin, and heterochromatin alterations may represent a driving force of human aging. Science, this issue p. 1160; see also p. 1093 Stabilization of heterochromatin by WRN protein safeguards human mesenchymal stem cells from aging. [Also see Perspective by Brunauer and Kennedy] Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina–heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.
Low Level of Her-2 Locus Amplification by Fluorescent In Situ Hybridization Does Not Correlate with Her-2 Protein Overexpression by Immunohistochemistry in Barrett's Esophagus

An accurate evaluation of the Her-2 status has important prognostic and therapeutic implications in many carcinomas. The aim of the study was to correlate Her-2 locus (17q11.2) amplification and chromosome 17 gains as assessed by fluorescent in situ hybridization (FISH) with Her-2 protein overexpression by immunohistochemistry (IHC) in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). We analyzed 34 patients with Her-2 amplification and/or chromosome 17gains using FISH on brush cytology specimens. Seven patients (21%) showed high Her-2 locus amplification (Her-2: Cep17 ≥ 5 : 1), 5 (15%) showed low Her-2 locus amplification (Her-2: Cep17 ≥ 2 < 5 : 1), and 22 (65%) displayed gains of chromosome 17 only. Further, we confirmed Her-2 amplification on corresponding biopsies that were taken at the same occasion as the cytologybrushings. Then, we compared the FISH results with IHC data obtained from the corresponding biopsies and showed that low level of Her-2 amplification does not correlate with Her-2 protein overexpression (score +3/+2; P = 1), in contrast to the high amplification level (P = .001). Thus, in our population of BE and EAC patients, low level of Her-2 amplification does not result in detectable level of Her-2 protein as assessed by IHC.
Baldness and testicular cancer: the EPSAM case–control study

The etiology of testicular cancer is largely unexplained. Research has mainly focused on prenatal exposures, especially to sex hormones, while less attention has been paid to exposures that may act also postnatally. As baldness has been previously associated with testicular cancer risk we focused on baldness and body hairiness, which are both associated with androgen activity. We used data of the Postnatal Exposures and Male Health (EPSAM) study, a case–control study on testicular cancer conducted in the Province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Information was collected using mailed questionnaires. Analyses included 255 cases and 459 controls. We calculated ORs and 95% CIs to estimate testicular cancer risk among those who developed baldness and among those with body hairiness. We found an inverse association between testicular cancer and baldness (OR: 0.67, 95% CI: 0.46–0.98) and body hairiness (OR: 0.78, 95% CI: 0.53–1.16), although the latter had wider CIs. The inverse association between baldness and testicular cancer is consistent with the results from previous studies. These results suggest that androgens activity may influence testicular cancer risk.
An Unusual Burst from Soft Gamma Repeater SGR 1900+14: Comparisons with Giant Flares and Implications for the Magnetar Model

The soft gamma-ray repeater SGR 1900+14 entered a remarkable phase of activity during the summer of 1998. This activity peaked on 1998 August 27, when a giant periodic γ-ray flare resembling the famous 1979 March 5 event from SGR 0526-66 was recorded. Two days later (August 29), a strong, bright burst was detected simultaneously with the Rossi X-Ray Timing Explorer (RXTE) and the Burst and Transient Source Experiment (BATSE). This event reveals several similarities to the giant flares of August 27 and March 5 and shows a number of unique features not previously seen in SGR bursts. Unlike typically short SGR bursts (duration ~0.1 s), this event exhibits a 3.5 s burst peak that was preceded by an extended (~1 s) complex precursor, and followed by a long (~103 s) pulsating tail modulated at the 5.16 s stellar rotation period. Spectral analysis shows a striking distinction between the spectral behavior of the precursor, main peak, and long tail. While the spectrum is uniform during the peak, a significant hard-to-soft spectral evolution is detected in both the precursor and tail emissions. Temporal behavior shows a sharp rise (~10 ms) at the precursor onset, a rapid cutoff (~17 ms) at the end of the burst peak, and a gradual decay (~17 minutes) of the pulsating tail. The tail pulsations show a simple pulse profile that did not evolve with time. The contrasted spectral and temporal signatures of the event suggest that the precursor, main peak, and extended tail are produced by different physical mechanisms, and that the observed tail represents a new emission component from SGRs. We discuss these features and their implications in the context of the magnetar model. The bright 3.5 s component is consistent with a very hot (kT ~ 1 MeV) trapped fireball, and the precursor with magnetospheric emission in which the radiating particles are heated more continuously. Less than 1% of the fireball energy will be conducted into the exposed surface of the neutron star, thereby dissociating heavy elements and even helium, and inducing rapid transformations between neutrons and protons. The extended "afterglow" tail of the August 29 burst is consistent with a cooling hot spot of small area (~13 km2), and indicates that the energy release in an SGR burst is strongly localized.
Pulmonary Vascular Resistance as Assessed by Bicycle Stress Echocardiography in Patients With Atrial Septal Defect Type Secundum

Background— Volume overload of the pulmonary circulation in patients with atrial septal defect (ASD)-type secundum causes pulmonary vascular disease over a long period of time. This study aimed at (1) evaluating pulmonary vascular resistance (PVR) and (2) investigating the relation between PVR and exercise capacity in patients with open and closed ASD. Methods and Results— Forty-six patients with ASD-type secundum (18 open, 28 closed) and 20 age-matched controls were enrolled. All underwent standard and symptom-limited bicycle stress echocardiography and cardiopulmonary exercise testing. PVR was calculated as the slope of a pulmonary artery systolic pressure (PAP)-flow plot or as the ratio of PAP to cardiac output (total PVR). The slope of PAP-flow was higher in patients with open (5.1±2.2 versus 3.0±0.8 mm Hg/L per min; P=0.002) and closed ASD (4.0±1.7 versus 3.0±0.8 mm Hg/L per min) compared with controls. In patients with an open ASD, total PVR did not change from rest to peak exercise. In patients with a closed ASD and controls, total PVR decreased from rest to peak exercise. However, in patients with an ASD closed later in life (≥34 years, median age at repair), the slope of PAP-flow was higher (5.1±1.4 versus 3.0±0.8 mm Hg/L per min; P<0.0001), but total PVR did not change from rest to peak exercise. Peak oxygen consumption correlated inversely with the slope of the PAP-flow plots in patients with open (P=0.013) and closed ASD (P=0.005). Conclusions— In patients with an open ASD, the slope of PAP-flow was higher and total PVR did not change from rest to peak exercise. In patients with an ASD closed later in life, the slope of PAP-flow was higher and total PVR did not change from rest to peak exercise, indicating altered pulmonary hemodynamics in these patients.
Impairment of recognition memory with, but not without, conscious recollection in schizophrenia.

OBJECTIVE To test the hypothesis that there is a link between the memory deficit associated with schizophrenia and an impairment of consciousness, an experiential approach was used to assess recognition memory and awareness in schizophrenic patients and normal subjects. METHOD On a recognition memory task with low- and high-frequency words, the schizophrenic (N = 30) and normal (N = 30) subjects gave "remember" responses to recognized items that were accompanied by conscious recollection and "know" responses to items that were recognized on the basis of familiarity without any recollective experience. RESULTS Schizophrenia selectively impaired recognition based on recollective experience, as measured by "remember" responses, but had no effects on "know" responses. In the comparison group, low-frequency words, relative to high-frequency words, enhanced conscious recollection but not familiarity. The schizophrenic patients did not display the same word-frequency effect. CONCLUSIONS These results indicate that schizophrenia affects differentially two means of access to the personal past: it impairs recognition memory with, but not without, conscious recollection. They suggest that the impairment of conscious recollection observed in schizophrenic patients could be due to a failure of elaborative processing of information.