Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of renal function in liver transplant recipients receiving daclizumab (Zenapax), mycophenolate mofetil, and a delayed, low‐dose tacrolimus regimen vs. a standard‐dose tacrolimus and mycophenolate mofetil regimen: A multicenter randomized clinical trial

Posttransplant chronic renal failure, secondary to calcineurin inhibitor agents, is emerging as a major problem in liver transplantation. We report a randomized clinical trial comparing daclizumab, delayed low‐dose tacrolimus (target trough level 4‐8 ng/mL, starting day 4‐6), Investigational Arm (n = 72), to standard tacrolimus induction/maintenance dosing, Standard Arm (n = 76), with mycophenolate mofetil and tapering corticosteroids in both study arms. The end‐points were renal function indicated by the Modification of Diet in Renal Disease (MDRD). There was no significant difference in patient survival (86.6% Investigational Arm vs. 92.9% Standard Arm; P = 0.21) or acute rejection (23.2% vs. 27.7%, respectively; P = 0.68). Statistically significant differences in median glomerular filtration rate (GFR) were found in favor of the Investigational Arm. With the CG equation, the GFR at the end of the first week was 110.7 vs. 89.6 mL/min (P = 0.019) without significant differences thereafter. With the MDRD, statistically significant differences extended to the first posttransplant month (86.8 vs. 70.1 mL/min/1.73 m2; P < 0.001) with and was seen at month 6 (75.4 vs. 69.5 mL/min/1.73 m2; P = 0.038). In conclusion, delayed low‐dose tacrolimus, in combination with daclizumab and mycophenolate mofetil, preserves early renal function post–liver transplantation without the cost of increased acute rejection. (Liver Transpl 2005;11:1064–1072.)
Clinical effects and toxicity of interleukin‐2 in patients with cancer

Interleukin‐2 (IL‐2) is a 15,000 dalton glycoprotein produced naturally by human T‐cells during an immune response. IL‐2 has been demonstrated to have substantial activity alone or in combination with the adoptive transfer of lymphokine‐activated killer cells in murine tumor models. IL‐2 derived from both natural (Jurkat human T‐cell tumor) and recombinant (Escherichia coli) sources has been studied in Phase I protocols designed to evaluate toxicity in patients with a variety of solid tumors and to ascertain improvement in clinical parameters and immunologic status. A total of 16 patients (7 with acquired immune deficiency syndrome [AIDS] and 9 with non‐AIDS malignancies) were treated with Jurkat derived IL‐2. The total maximum dose (1.3 × 105 U/kg) was limited only by supply of this reagent. A total of 25 patients have been treated with recombinant IL‐2 (RIL‐2) alone. Dose‐limiting toxicity manifested by marked malaise and weight gain was achieved with doses of RIL‐2 of 106 U/kg as a single bolus or 3000 U/kg/hr. IL‐2 could be administered intraperitoneally with similar toxicity. Minimal renal or hepatic toxicity was demonstrated. Hematologic toxicity was limited to mild anemia (25/25), thrombocytopenia (10/25), and marked reversible eosinophilia (15/25). Pronounced weight gain greater than 2 kg (16/25) occurred in most patients, primarily those who received cumulative doses of greater than 1–3 × 105 U/kg of IL‐2. The weight gain amounted to as much as 10% to 20% of the pretreatment weight over 3 weeks of treatment and limited our ability to give higher doses. Two partial responses (>50% decrease in cross sectional diameters) were seen in two patients with melanoma metastatic to the lung.
Effect of increased dosages of amoxicillin in treatment of experimental middle ear otitis due to penicillin-resistant Streptococcus pneumoniae

A gerbil model of acute middle ear otitis was used to evaluate the efficacy of increased dosages of amoxicillin in eradicating infection induced by penicillin-resistant Streptococcus pneumoniae. Three different strains were used: (i) a serotype 23 penicillin-susceptible strain; (ii) a serotype 23 penicillin-resistant strain (MIC of penicillin, 2 micrograms/ml); and (iii) a serotype 19 highly penicillin-resistant strain (MIC of penicillin, 4 to 8 micrograms/ml). Animals were inoculated bilaterally with 10(7) CFU per ear by transbulla challenge and treated 2 to 4 h postinfection by amoxicillin administrated subcutaneously. The course of the disease was monitored bacteriologically on days 2, 4, and 8 postinfection. The three strains had a similar pathogenicity in untreated animals in terms of the duration of the disease, bacterial counts in middle ear (ME) fluid, and systemic complications. Infection due to the penicillin-susceptible strain was cured after two injections of 2.5 mg/kg of body weight. No bacteria were recovered at day 2 after two injections at 10 and 25 mg/kg with the penicillin-resistant and highly penicillin-resistant strains, respectively. Under these experimental conditions, increased does of amoxicillin consistent with MICs were able to clear ME infection. Pharmacokinetic parameters of amoxicillin in serum and ME fluid were within the clinical range at the doses used in the study.
Glycosides derived from Hemidesmus indicus R. Br. root inhibit adherence of Salmonella typhimurium to host cells: receptor mimicry

For centuries, indigenous plants have been used against enteritis but their molecular targets and mode of action remain obscure. The present study was carried out to elucidate the protective and therapeutic role, if any, of glycosides from Hemidesmus indicus against S. typhimurium‐induced pathogenesis. Studies were carried out in a human intestinal cell line (Int 407) and a murine macrophage cell line (P388D1) in order to evaluate its potency in local as well as systemic infections. The inhibitory role of the glycosides present in Hemidesmus indicus root extract (GHI) were tested by pre‐coating the cells (both Int 407 and P388D1) with GHI prior to infection, and by neutralizing the wild‐type bacteria with GHI before cell infection. In both cases, GHI protected the host cells from the cytotoxic effects of the wild S. typhimurium. This suggests that the biologically significant sugars (hexose, hexosamine, fucose and sialic acid etc) present in GHI might be mimicking host cell receptor saccharides and thereby blocking the bacterial ligands from binding to the host cells. Int 407 cells infected with wild‐type bacteria had a diffused adherence pattern after 4 h incubation, but this typical character was not observed in cells infected with GHI‐treated bacteria and the cells were normal in appearance at 4 h. After 18 h cells infected with wild‐type bacteria were hypertrophoid with a disintegrated membrane and wrapped in a bacterial coat, whereas cells infected with treated bacteria had comparatively less morphological changes and few defective shrunken rods adhered locally. This suggests that the glycosides can change the adherence pattern of S. typhimurium from diffused to local. Treated bacteria had less adherence and invasion capability in Int 407 as well as P388D1 cells. The results show the decreased ability of adherence of GHI‐treated S. typhimurium was due to a loss of surface hydrophobicity. A nonspecific binding between S. typhimurium and the glycosides was confirmed using ELISA. In summary, the glycosides of H. indicus root inhibited S. typhimurium induced pathogenesis nonspecifically, by reducing bacterial surface hydrophobicity and perhaps also by mimicking host cell receptors, thereby blocking its attachment to host cell and further pathological effects. Copyright © 2006 John Wiley & Sons, Ltd.
[Relationship between deliberate self-harm and suicidal behaviors in college students].

OBJECTIVE To describe the prevalence of deliberate self-harm (DSH) and suicidal behaviors (SIB) as well as the relationship between them in a college student population. METHODS A total of 4063 medical students were selected under the cluster sampling method in Anhui province. Data were analyzed by Pearson Chi-square and logistic regression. RESULTS A total of 4063 (13.4%) students reported that they had deliberately harmed themselves during the past 12 months. The acts of DSH with 1 and more than or equal to 2 times occurrence accounted for 3.7% and 9.6% among all the respondents. The act of DSH was significantly higher among boys than that among girls. Rates of suicide ideation, suicide plan, attempted suicide and SIB in the last year were 4.5%, 1.4%, 0.6% and 4.9%, respectively. However no statistically significant difference was found in different sex. Students in the DSH group that with SIB were found to have lower positive coping levels (OR=0.5, 95%CI: 0.3-0.8), getting less support from friends (3-5 vs. less than or equal to 2: OR=0.6, 95%CI: 0.3-0.9; more than or equal to 6 vs. less than or equal to 2: OR=0.4, 95%CI: 0.2-0.8), with higher negative coping levels (OR=2.1, 95%CI: 1.2-3.7), having more serious depressive symptoms (OR=2.9, 95%CI: 1.6-5.2) and anxiety symptoms (OR=2.2, 95%CI: 1.2-3.8), having more serious sleeping problems (OR=1.7, 95%CI: 1.1-2.8) and perceived fat (fat vs. moderate: OR=2.0, 95%CI: 1.1-3.6) than the DSH group without SIB. The rates of SIB in students with DSH behavior were significantly higher than those in students without those behaviors (OR=4.7, 95%CI: 3.5-6.4). Psychosocial variables could attenuate the relationship between the DSH status and suicidal events (OR=3.3, 95%CI: 2.4-4.5). The DSH frequency exhibited a curvilinear relationship to SIB (OR=3.1-10.0) and psychosocial variables also attenuated this relationship (OR=2.4-5.9). CONCLUSION It was well known that SIB was not a suicidal gesture but our findings suggested that the presence of DSH might trigger the suicidal attempts.
Oropharyngeal crowding and obesity as predictors of oral appliance treatment response to moderate obstructive sleep apnea.

BACKGROUND Oral appliances are increasingly prescribed for patients with moderate obstructive sleep apnea (OSA) instead of nasal CPAP. However, the efficacy of oral appliances varies greatly. We hypothesized that oral appliances were not efficacious in patients with moderate OSA who were obese with oropharyngeal crowding. METHODS Japanese patients with moderate OSA were prospectively and consecutively recruited. The Mallampati score (MS) was used as an estimate of oropharyngeal crowding. Follow-up polysomnography was performed with the adjusted oral appliance in place. Responders were defined as subjects who showed a follow-up apnea-hypopnea index (AHI) of < 5 with > 50% reduction in baseline AHI. RESULTS The mean baseline AHI was reduced with an oral appliance from 21 ± 4 to 9.8 ± 8 in 95 subjects. Thirty-five patients were regarded as responders. Logistic regression analyses revealed that both MS and BMI could individually predict the treatment outcome. When the cutoff value of BMI was determined to be 24 kg/m2 based on a receiver operating characteristic curve, 53 obese patients (ie, BMI > 24 kg/m2) with an MS of class 4 were indicative of treatment failure with a high negative predictive value (92) and a low negative likelihood ratio (0.28). CONCLUSIONS We conclude that patients with moderate OSA who are obese with oropharyngeal crowding are unlikely to respond to oral appliance treatment. This simple prediction can be applied without the need for any cumbersome tools immediately after the diagnosis of OSA.
Survival after liver transplantation in the United States: A disease‐specific analysis of the UNOS database

Our goal was to describe disease‐specific survival and the clinical variables that predict survival in a large national cohort of adult liver transplant recipients. Data on 17,044 adult patients who received an initial orthotopic liver transplant between 1990 and 1996 with follow‐up through 1999 was obtained from the United Network for Organ Sharing (UNOS). Disease‐specific Kaplan‐Meier survival plots and Cox Proportional Hazards models were estimated, and differences in the clinical characteristics of patients at the time of transplantation by disease were examined. Overall posttransplant survival currently exceeds 85% in the first year and is approaching 75% at 5 years. Unadjusted Kaplan‐Meier survival is improved for recipients who are younger, female, and in better clinical condition. Survival is a function of disease and level of illness: cancer, fulminant liver failure, alcoholic liver disease, and the hepatitidies have the poorest prognosis, while primary billiary cirrohsis and sclerosing cholangitis have the best. Recipients who were outpatients before transplantation have longer survival than those transplanted from the hospital or intensive care unit. Although the model for end‐stage liver disease (MELD) score was designed to predict pretransplant survival, patients with higher MELD scores have poorer posttransplant survival, but the MELD score is less predictive than the specific disease. Differences in disease‐specific survival are partially explained by differences in disease severity at the time of transplantation. In conclusion, Disease‐specific survival models indicate that there remains tremendous variability in survival as a function of underlying liver disease. However, a significant portion of the difference in survival between diseases arises from differences in clinical characteristics at the time of transplantation. (Liver Transpl 2004;10:886–897.)
Chromatographic estimation of drug disposition properties by means of immobilized artificial membranes (IAM) and C18 columns.

Chromatographic retention measurement in immobilized artificial membranes (IAMs) is considered a fast and reliable method to predict biological properties (drug distribution) because of the IAM structure, which consists of phospholipid analogues bonded covalently to silica particles. A new parameter (d) is proposed to estimate the similarity between IAM columns, conventional HPLC columns, and drug distribution systems, and thus the performance of chromatographic systems to predict drug distribution. An IAM.PC. DD2 column has been used for this study, together with two XTerra columns (MSC18 and RP18), at several acetonitrile-water mobile phases. According to the d parameter, good correlations should be obtained between chromatographic systems (both IAM and C18) and octanol-water partition coefficient (log P), and thus both types of columns could be used to obtain log P values. The IAM.PC. DD2 system shows a close similarity to human skin partition, tadpole narcosis, and blood-brain permeability processes, showing that it can be useful as a model for these biological processes. Controversially, it is shown that human skin permeation is more similar to C18 partition than to IAM partition. Other biological processes such as blood-brain distribution and tissue-blood partition show a poor similarity to IAM and C18 systems, demonstrating that estimation of these drug distribution processes by chromatographic measurements may not be adequate.
Spatial resolution recovery utilizing multi-ray tracing and graphic processing unit in PET image reconstruction

Depth-of-interaction (DOI) poses a major challenge for a PET system to achieve uniform spatial resolution across the field-of-view, particularly for small animal and organ-dedicated PET systems. In this work, we implemented an analytical method to model system matrix for resolution recovery, which was then incorporated in PET image reconstruction on a graphical processing unit platform, due to its parallel processing capacity. The method utilizes the concepts of virtual DOI layers and multi-ray tracing to calculate the coincidence detection response function for a given line-of-response. The accuracy of the proposed method was validated for a small-bore PET insert to be used for simultaneous PET/MR breast imaging. In addition, the performance comparisons were studied among the following three cases: 1) no physical DOI and no resolution modeling; 2) two physical DOI layers and no resolution modeling; and 3) no physical DOI design but with a different number of virtual DOI layers. The image quality was quantitatively evaluated in terms of spatial resolution (full-width-half-maximum and position offset), contrast recovery coefficient and noise. The results indicate that the proposed method has the potential to be used as an alternative to other physical DOI designs and achieve comparable imaging performances, while reducing detector/system design cost and complexity.
A self-rating to measure subjective effects of neuroleptic drugs, relationships to objective psychopathology, quality of life, compliance and other clinical variables

The benefit of neuroleptic drugs in the treatment of schizophrenic patients is objectively beyond any doubt. However, most patients discontinue their neuroleptic drugs within some months. This low compliance might be caused by the lack of insight into the disease and the necessity of therapy. Also of major importance are adverse effects, not restricted to motor symptoms, but also affecting cognition and emotion. They are often too subtle to be detected by objective examination, but reported by patients who complain of a reduced quality of life with restrictions of emotionality, straight thinking and spontaneity. This syndrome, similar to negative symptoms of schizophrenia, has been named 'pharmacogenic depression' or 'neuroleptic-induced deficit syndrome'. To investigate this issue of major clinical relevance, a self-rating scale was developed to measure subjective well-being under neuroleptic treatment (S WN). First analyses indicate good practicability, reliability, validity and sensitivity. Data obtained from 280 remitted schizophrenic patients showed that the S WN was significantly correlated to objective psychopathology (Positive and Negative Symptom Scale, PANSS; r=-035), quality of life (r=0.60) and other self-ratings of mood states [Profile of Mood Scale (POMS), Self-rating Depression Scale (SDS), Befindlichkeits Scale (BFS); r= 0.25-0.75]. A repeated application after 3 months in 53 patients did not show any change in SWN in those with constant neuroleptic medication, but there were marked alterations if the dosage or the drug was changed. The SWN in 28 patients treated with clozapine because of therapy resistance or major side effects was, despite negative selection, significantly better (t= 1.79, p=0.03) than in 38 patients under classical neuroleptics. Moreover, even at dismissal, patients who were non-compliant 4-6 months later (n= 14) differed significantly (t=3.21, p=0.02) in SWN, but not in PANSS, from those who remained compliant (n=34). These data indicate that the SWN is a useful tool for investigating a hitherto neglected psychopathological dimension. Subjective effects of neuroleptics are measurable, affect patients' quality of life and should be considered more thoroughly in clinical routine as well as in clinical trials of potential neuroleptic drugs.
A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013.

OBJECTIVE This literature review assessed the burden of treatment-resistant depression in the United States by compiling published data about the clinical, societal, and economic outcomes associated with failure to respond to one or more adequate trials of drug therapy. METHODS PubMed and the Tufts Cost-Effectiveness Analyses Registry were searched for English-language articles published between January 1996 and August 2013 that collected primary data about treatment-resistant depression. Two researchers independently assessed study quality and extracted data. RESULTS Sixty-two articles were included (N=59,462 patients). Patients with treatment-resistant depression had 3.8±2.1 prior depressive episodes and illness duration of 4.4±3.3 years and had completed 4.7±2.7 unsuccessful drug trials involving 2.1±. 3 drug classes. Response rates for treatment-resistant depression were 36%±1%. A total of 17%±6% of patients had prior suicide attempts (1.1±.2 attempts per patient). Quality-of-life scores (scale of 0-1, with 0 indicating death and 1 indicating perfect health) for patients with treatment-resistant depression were . 41±. 8 and . 26±. 8 points lower, respectively, than for patients who experienced remission or response. Annual costs for health care and lost productivity were $5,481 and $4,048 higher, respectively, for patients with treatment-resistant versus treatment-responsive depression. CONCLUSIONS Treatment-resistant depression exacts a substantial toll on patients' quality of life. At current rates of 12%-20% among all depressed patients, treatment-resistant depression may present an annual added societal cost of $29-$48 billion, pushing up the total societal costs of major depression by as much as $106-$118 billion. These findings underscore the need for research on the mechanisms of depression, new therapeutic targets, existing and new treatment combinations, and tests to improve the efficacy of and adherence to treatments for treatment-resistant depression.
Sex and the Risk of AKI Following Cardio-thoracic Surgery: A Meta-Analysis.

BACKGROUND AND OBJECTIVES Being a woman is a well established risk factor for the development of cardiothoracic surgery-associated AKI. In striking contrast, women are less likely to develop AKI associated with noncardiac surgical procedures than men. In an attempt to ascertain why being a woman might be protective for ischemic AKI after general surgery but deleterious in patients undergoing cardiothoracic surgery, we examined cardiothoracic surgery-associated AKI in greater detail. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a systematic review and meta-analysis of cardiothoracic surgery-associated AKI studies published between January of 1978 and December of 2015 to further explore the relationship between sex and cardiothoracic surgery-associated AKI. RESULTS Sixty-four studies were identified that provided sex-specific data regarding the incidence of cardiothoracic surgery-associated AKI among 1,057,412 subjects. Using univariate analysis, women were more likely than men to develop AKI postoperatively (odds ratio, 1.21; 95% confidence interval, 1.09 to 1.33; P<0.001). However, when the analysis was restricted to the 120,464 subjects reported in 29 studies that used the Acute Kidney Injury Network criteria, the RIFLE criteria, or the Kidney Disease Improving Global Outcomes criteria to define AKI, there was no significant sex-related difference in risk. Seventeen studies used multivariate analysis to assess risk factors for cardiothoracic surgery-associated AKI and provided sex-specific odd ratios. Among the 1,587,181 individuals included in these studies, the risk of developing cardiothoracic surgery-associated AKI was not significantly associated with sex (odds ratio, 1.04; 95% confidence interval, 0.92 to 1.19; P=0.51). However, when the analysis was restricted to the 5106 subjects reported in four studies that used the Acute Kidney Injury Network criteria to define AKI, the risk of developing AKI was significantly lower in women compared with in men (odds ratio, 0.75; 95% confidence interval, 0.65 to 0.87; P<0.001). CONCLUSIONS Our systematic review and meta-analysis contradict the generally held consensus that being a woman is an independent risk factor for the development of cardiothoracic surgery-associated AKI.