Miracle-dz/UniFAR-FTUs huggingface dataset:
Overview of Antiretroviral Agents in 2005

To date, 25 antiretroviral agents (including fixed-dose combinations) have gained approval by the Food and Drug Administration and are currently available on the market for the treatment of HIV-1 infection. New protease inhibitors, atazanavir sulfate (Reyataz) and fosamprenavir (Lexiva), were licensed, in addition to the nucleoside analogue reverse transcriptase inhibitor (NRTI) emtricitabine (Emtriva) and 2 fixed-dose NRTI combinations, emtricitabine/tenofovir disoproxil fumarate (Truvada) and lamivudine/abacavir (Epzicom). These newly licensed antiretroviral agents allow for lower pill burden and dosing schedule simplification, and some agents such as atazanavir sulfate are associated with improved lipid profile in comparison to other currently marketed protease inhibitors. In addition, a new class of anti-retroviral agents, entry inhibitors, of which a subclass exists called fusion inhibitors with its representative member, enfuvirtide (Fuzeon), which is currently the only available drug in its class, was marketed almost 2 years ago. Despite a remarkable progress in the treatment of HIV infection noted during the past decade, significant challenges to therapy such as tolerability issues and emergence of drug-resistant strains remain. Therefore, new antiretroviral drug development has focused on a design of drugs that work against the resistant strains of HIV and/or have a novel mechanism of action.
Linear and nonlinear relationships between cognitive subdomains of ability discrepancy and Alzheimer's disease biomarkers.

OBJECTIVE Substantial research indicates that fluid and crystallized abilities are highly correlated throughout the adult life span. However, recent proposals suggest that a large discrepancy between these two abilities, defined as crystallized performance minus fluid performance, indicates heightened risk for Alzheimer's disease (AD). METHOD In 266 cognitively healthy older adults, the present study tested linear and quadratic relationships between an ability discrepancy score and early AD neuropathology indexed via in vivo measures of beta-amyloid deposition and cortical thickness in AD-vulnerable regions. We also tested the extent that alternative forms of this ability discrepancy measure (e.g., subdomain discrepancies, verbal-visual discrepancies) and an episodic memory composite might also be sensitive markers of early AD pathology. RESULTS An overall ability discrepancy was linearly and positively correlated with beta- amyloid. A quadratic relationship was found between the overall ability discrepancy score and cortical thickness such that a small positive correlation was found at lower discrepancy levels (fluid > crystallized), but at higher discrepancy levels (crystallized > fluid) a negative relationship was found (i.e., an inverted-U pattern). Similar patterns were found across each subdomain of cognition, but the effects were weaker than the overall ability discrepancy score. Importantly, inclusion of episodic memory (the gold standard) did not alter any of the effects, suggesting that an ability discrepancy confers unique predictiveness of AD biomarkers. CONCLUSIONS These findings replicate previous findings and increase the confidence in their usefulness to predict AD biomarkers. Longitudinal validation is needed to clearly relate an ability discrepancy to specific stages of preclinical AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
An NIR‐based PAT approach for real‐time control of loading in Protein A chromatography in continuous manufacturing of monoclonal antibodies

Control of column loading in Protein A chromatography is a crucial part of development of robust and flexible process platforms for continuous production of monoclonal antibody (mAb) products. In this paper, we propose a control system that uses near infrared spectroscopy (NIRS) flow cells to accomplish the above. Two applications have been demonstrated using a periodic counter‐current continuous chromatography setup. The first application involves use of single NIR flow cell before the inlet of the loading column to measure the concentration of mAb in the harvested broth. Measurement was in real‐time (every 3 s) and within ±0.05 mg/ml, significantly better than making UV‐based concentration estimations. The second application involved use of an additional NIR flow cell at the outlet of the loading column to measure column breakthrough in real time. The concentration data was transferred to a Python‐based monitoring and control algorithm layered over a Cadence BioSMB system. The program could successfully run a three‐column periodic counter current method on the BioSMB whereas controlling loading to ensure optimal resin utilization in each loading cycle phase based on precharacterized dynamic binding capacity models, whereas maintaining periodic elutions. The system was tested with multiple perturbations in harvest concentration, modeled after deviations that could arise downstream of a perfusion cell culture system. The results show that the proposed control is a spectroscopy‐based process analytical technology tool that facilitates real time monitoring and control of loading in process chromatography. It is adaptable to any continuous chromatography equipment and is very well suited for implementation in a continuous mAb production train.
Linking parental mediation practices to adolescents’ problematic online screen use: A systematic literature review

Background and aims To remedy problematic Internet use (PIU) and problematic online gaming (POG) in adolescents, much is expected from efforts by parents to help youths to contain their screen use. Such parental mediation can include (a) refraining from acting, (b) co-viewing or co-gaming with the teen, (c) active mediation, and (d) restrictive mediation. We evaluated if parental mediation practices are linked to PIU and POG in adolescents. Methods For a systematic literature review, we searched for publications presenting survey data and relating parental mediation practices to levels of PIU and/or POG in adolescents. The review’s selection criteria were met by 18 PIU and 9 POG publications, reporting on 81.002 and 12.915 adolescents, respectively. We extracted data on gaming problems, mediation interventions, study design features, and sample characteristics. Results No type of parental mediation was consistently associated with lower or elevated problematic screen use rates in the adolescents. Refraining from parental mediation tended to aggravate screen use problems, whereas active mediation (talking to the teen) may mitigate such problems in PIU, but less clearly in POG. The link of restrictive mediation with problematic screen use varied from positive to negative, possibly depending on type of restriction. In both PIU and POG, family cohesion was related to lower rates of the problem behavior concerned and family conflict to higher rates. Discussion and conclusions Parental mediation practices may affect problematic screen use rates for better or worse. However, research of higher quality, including observations of parent-teen interactions, is needed to confirm the trends noted and advance the critical issue of the possible association between PIU, POG, and family interactions.
Performance of liver biomarkers, in patients at risk of nonalcoholic steato-hepatitis, according to presence of type-2 diabetes

Supplemental Digital Content is available in the text. Objective There is a controversy about the performance of blood tests for the diagnostic of metabolic liver disease in patients with type-2-diabetes in comparison with patients without type-2-diabetes. These indirect comparisons assumed that the gold-standard is binary, whereas fibrosis stages, steatosis and nonalcoholic-steato-hepatitis (NASH) grades use an ordinal scale. The primary aim was to compare the diagnostic performances of FibroTest in type-2-diabetes vs. controls matched on gender, age, fibrosis stages and obesity, and taking into account the spectrum effect by Obuchowski measure. Methods Data were retrospectively compared among patients prospectively included, with simultaneous biopsy and blindly assessed FibroTest, SteatoTest-2 and NashTest-2. The secondary aim was to construct an index (SpectrumF3F4-Index) to predict an adjusted-area under the receiver operating curve (AUROC) for F3F4 diagnosis from the prevalences of fibrosis stages, permitting to reduce the spectrum effect when performances of FibroTest, transient elastography and magnetic resonance elastography are indirectly compared. Results In 505 patients at risk of NASH, the Obuchowski measures [95% confidence interval (CI)] of FibroTest, SteatoTest-2 and NashTest-2 were all equivalent in 136 type-2-diabetes cases vs. 369 matched controls: 0.871 (0.837–0.905), vs. 0.880 (0.879–0.881), 0.835 (0.797–0.873) vs. 0.806 (0.780–0.832) and 0.829 (0.793–0.865) vs. 0.855 (0.829–0.869), respectively. Standard-AUROCs (95% CI) were 0.932 (0.898–0.965), 0.872 (0.837–0.907) and 0.834 (0.699–0.969) and reduced after adjustment by SpectrumF3F4-Index to 0.794 (0.749–0.838), 0.767 (0.750–0.783) and 0.773 (0.725–0.822) for transient, magnetic resonance elastography and FibroTest, respectively. Conclusions When compared by Obuchowski measures, the performances of tests were not different in patients with T2-diabetes vs. patients without T2-diabetes. When individual data are not available, adjusted-AUROCs reduced the spectrum effect.
Crack cocaine smoke on pregnant rats: Maternal evaluation and teratogenic effect

This study aimed to evaluate maternal toxicity, teratogenic, and placental oxidative effects resulting from the exposure of rats to crack cocaine smoke during pregnancy. Pregnant rats were exposed either to the smoke of crack and ashes (Crack) or to the smoke of ashes alone, nonexposed or pair-fed with the Crack group. Crack group was exposed to the smoke resulting from the burning of 250 mg of crack for 10 min, twice a day, from 7 days prior to mating until cesarian on gestational day 20. Placental oxidative stress and classical parameters of maternal and fetal evaluation were studied, in addition to the morphometric analysis of the fetal metamers. Even in the absence of changes in body weight gain and feed intake, crack altered the reproductive performance of dams. Exposure to the drug promoted late closure of the fetal fontanel. Furthermore, the morphometric study of the brain mass (BM)/skull cap ratio revealed a decrease in the BM of the fetuses exposed to the drug. Exposure to crack has an oxidative potential in fetal development, since exposure to the drug promoted placental lipid peroxidation. Our study showed that daily exposure to crack, even in lower frequency than that performed by users, has a teratogenic potential.
Psychological distress trajectories in chronic physical health conditions.

OBJECTIVE The onset of a chronic health condition (CHC) can have a severe impact on an individual's life, affecting mental and physical health. This study's goal was to investigate psychological distress trajectories starting from 1 year before to 4 years after the onset of a physical CHC. The specific aims were to identify the number and shape of longitudinal psychological distress trajectories and to test health-related, psychological, social, and demographic factors predicting these trajectories. METHOD Two samples were drawn from the Swiss Household Panel data set: a CHC sample (n = 361) and a 1-to-1 matched comparison sample of healthy individuals. Latent growth mixture modeling was used to identify psychological distress trajectories over 6 years. Factors predicting trajectories were then tested using multinomial logistic regression. RESULTS Four psychological distress trajectories were identified in the CHC sample: resilience (53.9%), chronic (22.2%), delayed (15.0%), and recovery (8.9%). In the comparison sample, two trajectories were identified: low psychological distress (90%) and elevated psychological distress (10%). Protective factors associated with resilient trajectory membership in the CHC sample were higher emotional stability, higher relationship satisfaction, and male gender. CONCLUSION Individuals living with a CHC had an increased risk of vulnerability compared with a sample of healthy individuals. This advocates awareness of mental health issues following the onset of a CHC. In this regard, biopsychosocial factors (gender, emotional stability, and relationship satisfaction) offer prevention and intervention opportunities for more vulnerable individuals. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
The role of adiponectin in ischemia -reperfusion injury in the type 2 diabetic heart

Cardiovascular disease (CVD) is the leading cause of death in the United States, and the risk and severity of CVD are increased with type 2 diabetes. However, the exact mechanisms that result in the enhanced association between CVD and type 2 diabetes have not been clearly elucidated. Inflammation and oxidative stress are strongly implicated in both diseases. In type 2 diabetes, there is a dysregulation of inflammatory mediators where an anti-inflammatory molecule adiponectin and a pro-inflammatory cytokine TNF-α are reduced and increased, respectively. Even lower plasma adiponectin concentrations are associated in type 2 diabetic patients with cardiovascular disease. Thus, adiponectin may be a significant link between the two diseases. The studies in this dissertation examined the in vivo cardioprotective actions of adiponectin and apocynin, a NADPH oxidase inhibitor, in the Zucker diabetic fatty (ZDF) type 2 diabetic model. A model of coronary artery occlusion was utilized to induce myocardial ischemiareperfusion (I/R) injury. The mechanisms of protective actions were assessed by measures of inflammation, oxidative stress and DNA damage. Further, in vitro actions of adiponectin in human whole blood were investigated. We found that in vivo treatments of adiponectin and apocynin significantly reduced myocardial infarction in the type 2 diabetic heart by 40% and 68%, respectively. The cardioprotective action of adiponectin was associated with 2 to 4 fold significant attenuations in several inflammatory characteristics, such as neutrophil adhesion molecule CD11b expression, myocardial adhesion molecule ICAM-1 expression, myocardial neutrophil accumulation and plasma
Physician-Modified Endograft With Double Inner Branches for Urgent Repair of Supraceliac Para-Anastomotic Pseudoaneurysm

Purpose: To demonstrate the feasibility of a physician-modified endograft (PMEG) with inner branches for 2 mesenteric arteries as an alternative to fenestrations or directional branches. Technique: A symptomatic 60-year-old man presented with supraceliac para-anastomotic pseudoaneurysm involving an antegrade aorta to celiac artery and superior mesenteric artery bypass. Since an off-the-shelf multibranched endograft was inappropriate, a Zenith Alpha thoracic stent-graft was modified with 2 inner branches fashioned of 8-mm Viabahn endoprostheses with preloaded guidewires. The procedure was technically successful, and the patient had no postoperative complications. Conclusion: Inner branches might offer an alternative to fenestrations or directional branches in patients with narrow aortas.
Idiopathic Normal Pressure Hydrocephalus: A Review And A Proposed Role For

IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS: A REVIEW AND A PROPOSED ROLE FOR PATIENT-REPORTED OUTCOMES. Conor W. Grady (Sponsored by Charles C. Matouk). Department of Neurosurgery, Yale University, School of Medicine, New Haven, CT. Despite nearly five decades of experience treating idiopathic normal pressure hydrocephalus (iNPH), there is still no consensus amongst care providers as to how to reliably identify patients with suspected iNPH who will benefit from shunt surgery, or how to measure post-operative symptom improvement. We performed a selective review of the literature, focusing especially on the role of neuroimaging in aiding in the diagnosis of iNPH, and the various clinical scales that have historically been used to assess outcome. Further, we tested the hypothesis that patient-reported outcomes (PROs) will demonstrate effectiveness of shunt surgery for the relief of iNPH symptoms consistent with that demonstrated through the application of clinical scales. To do this, we performed a retrospective analysis of one provider’s experience treating patients with suspected iNPH, scoring outcomes based on patient-reported change in symptom severity. All patients treated for suspected iNPH between January 2012 and January 2014 with at least one month of follow-up and documented responses to direct questioning about preversus post-surgical symptom severity were included. Twenty-one patients were included in total. 100% of patients reported improvement in at least one of the three cardinal symptoms of gait disturbance, urinary incontinence, or cognitive impairment following shunt implantation. Gait, urinary, and cognitive symptoms individually improved 95%, 84%, and 89%, respectively. There was a significantly higher rate of improvement in any (i.e. at least one) symptom domain using PROs compared to historical data obtained through evaluation with clinical scales. There was no statistically significant difference between improvements in each individual symptom domain. PROs produce results that are largely consistent with data obtained by clinical scales, and can be used as one metric of patient improvement following shunt surgery for iNPH.
Scaling the great wall: The impact of communication barriers on quality of psychiatric care in Chinese patients

Background: Racial and ethnic minorities (such as Chinese-speaking (CS)) are known to have less equitable access to mental health services than Caucasians. These disparities have a powerful influence on minority groups that already endure a greater burden from mental health needs. Aim: The aim was to identify perceived provider barriers to care for CS patients. Methods: The study involved an 11-item web-based survey to multidisciplinary health professionals in the department of psychiatry at a 75-bed teaching community mental health center. Results: More than half the respondents agreed that there are disparities in the management of CS versus non-CS patients primarily due to the language barrier (46%). However, older participants and participants who worked fewer hours per week in patient care were less likely to agree (rho = −.27, p = .05 and rho = .33, p = .015, respectively) that these perceived difficulties prevented them from caring for these patients. Conclusion: The study revealed that certain modifiable factors like the limited availability of interpreters and culturally appropriate services, rendering psychoeducation and forming therapeutic alliances with CS patients, posed the greatest challenges on inpatient units. In light of these findings, we aim to make recommendations to remediate concerns of limited provider availability by proposing ways to efficiently utilize current resources and advocate for better staffing to improve the overall well-being of this challenging patient subset.
Association of rs2234693 and rs9340799 polymorphisms of ESR1 gene in breast cancer of Mexican population.

PURPOSE The rs2234693 and rs9340799 ESR1 polymorphisms have shown contradictory results in studies of breast cancer (BC). The purpose of this study was to determine the frequency and association of ESR1 polymorphisms (rs2234693 and rs9340799) in BC patients of Mexican population. METHODS PCR was used to genotype rs2234693 and rs9340799 polymorphisms in the ESR1 gene in Mexican healthy subjects and breast cancer (BC) patients. RESULTS The frequency of cases and control groups of rs2234693 and rs9340799 polymorphisms in the ESR1 was similar, and none has shown any association with increased BC risk (p>0.05), although the association between the haplogenotypes (rs2234693 and rs9340799 polymorphisms) and BC patients with miscarriages [CTAG variant, adjusted odds ratio (OR) 1.83 (95%CI 1.17-2.86);p=0.011] and tobacco consumption [CCGG variant, adjusted OR 1.88 (95%CI 1.11-3.19);p=0.018] was evident. Also, the homozygous genotype TT [rs2234693, OR 1.49 (95%CI 1.02-2.19);p=0.042] and GG [rs9340799, OR 2.85 (95%CI 1.144-7.10);p=0.024] showed marginal association with BC, indicating that these factors may contribute significantly to the susceptibility of risk to BC. The TA haplotype was more common in controls than in CG. BC patients with a frequency around 0.71 among study groups, but without significant difference (p>0.05). CONCLUSION rs2234693 and rs9340799 polymorphisms in the ESR1 gene were not associated with susceptibility for BC. However, the haplogenotypes CTAG and CCGG of rs2234693 and rs9340799 polymorphisms could contribute significantly to the susceptibility of risk in BC positive at miscarriage and tobacco consumption in this sample population.
A case of phaeohyphomycosis caused by Exophiala oligosperma in a renal transplant patient successfully treated with posaconazole

Phaeohyphomycosis is an uncommon mycotic infection caused by dematiaceous fungi. We report a 53-year-old male who presented with phaeohyphomycosis on his upper extremities, 6 months after renal transplantation. Biopsy revealed pigmented moniliform hyphae and cultures grew Exophiala oligosperma. The lesions completely resolved after 3 months of treatment with posaconazole.
Outcomes of laparoscopic radical nephrectomy for elderly patients with localized renal cell carcinoma.

PURPOSE This study was to compare the short- and long-term outcomes of elderly versus middle-aged patients with localized renal cell carcinoma who had undergone laparoscopic radical nephrectomy. METHODS Between January 2012 and January 2018, a total of 54 patients aged 70 years and above with localized renal cell carcinoma (elderly group) underwent laparoscopic radical nephrectomy. The short- and long-term outcomes of these 54 patients were compared with those of 97 middle-aged patients (aged between 55 and 69 years; middle-aged group) who underwent laparoscopic radical nephrectomy due to localized renal cell carcinoma. RESULTS The age, Charlson's comorbidity index, and American Society of Anesthesiologists (ASA) score were higher in the elderly group than in the middle-aged group. Other preoperative baseline data did not show any statistically significant differences. The differences in short-term outcomes, including operative time, intraoperative blood loss, transfer rate, postoperative 30-day complication rate and severity of complication, and pathological data were not statistically significant between the elderly and middle-aged groups. Long-term follow-up results showed that the tumor recurrence rates were similar in the two groups. Overall and disease-free survival rates were similar in the two groups. Multivariate analysis showed that age was not an independent predictor for overall and disease-free survival rates. CONCLUSIONS Treatment with laparoscopic radical nephrectomy for elderly patients with localized renal cell carcinoma, could achieve short- and long-term outcomes, similar to those of middle-aged patients.